New Tool for Next-Generation Cancer Treatments using Nanodiamonds
A research team at Northwestern University has demonstrated a tool that can precisely deliver tiny doses of drug-carrying nanomaterials to individual cells.
The tool, called the Nanofountain Probe, functions in two different ways: in one mode, the probe acts like a fountain pen, wherein drug-coated nanodiamonds serve as the ink, allowing researchers to create devices by "writing" with it. The second mode functions as a single-cell syringe, permitting direct injection of biomolecules or chemicals into individual cells.
The research was led by Horacio Espinosa, professor of mechanical engineering, and Dean Ho, assistant professor of mechanical and biomedical engineering, both at the McCormick School of Engineering and Applied Science at Northwestern. Their results were recently published online in the scientific journal Small.
The probe could be used both as a research tool in the development of next-generation cancer treatments and as a nanomanufacturing tool to build the implantable drug delivery devices that will apply these treatments. The potential of nanomaterials to revolutionize drug delivery is emergent in early trials, which show their ability to moderate the release of highly toxic chemotherapy drugs and other therapeutics. This provides a platform for drug-delivery schemes with reduced side effects and improved targeting.
“This is an exciting development that complements our previous demonstrations of direct patterning of DNA, proteins and nanoparticles,” says Espinosa.
Using the Nanofountain Probe, the group injected tiny doses of nanodiamonds into both healthy and cancerous cells. This technique will help cancer researchers investigate the efficacy of new drug-nanomaterial systems as they become available.
The group also used the same Nanofountain Probes to pattern dot arrays of drug-coated nanodiamonds directly on glass substrates. The production of these dot arrays, with dots that can be made smaller than 100 nanometers in diameter, provides the proof of concept by which to manufacture devices that will deliver these nanomaterials within the body.
The work addresses two major challenges in the development and clinical application of nanomaterial-mediated drug-delivery schemes: dosage control and high spatial resolution.
In fundamental research and development, biologists are typically constrained to studying the effects of a drug on an entire cell population because it is difficult to deliver them to a single cell. To address this issue, the team used the Nanofountain Probe to target and inject single cells with a dose of nanodiamonds.
“This allows us to deliver a precise dose to one cell and observe its response relative to its neighbors,” Ho says. “This will allow us to investigate the ultimate efficacy of novel treatment strategies via a spectrum of internalization mechanisms.”
Beyond the broad research focused on developing these drug-delivery schemes, manufacturing devices to execute the delivery will require the ability to precisely place doses of drug-coated nanomaterials. Ho and colleagues previously developed a polymer patch that could be used to deliver chemotherapy drugs locally to sites where cancerous tumors have been removed. This patch is embedded with a layer of drug-coated nanodiamonds, which moderate the release of the drug. The patch is capable of controlled and sustained low levels of release over a period of months, reducing the need for chemotherapy following the removal of a tumor.
“An attractive enhancement will be to use the Nanofountain Probe to replace the continuous drug-nanodiamond films currently used in these devices with patterned arrays composed of multiple drugs,” Ho says. “This allows high-fidelity spatial tuning of dosing in intelligent devices for comprehensive treatment.”
“One of the most significant aspects of this work is the Nanofountain Probe’s ability to deliver nanomaterials coated with a broad range of drugs and other biological agents,” Espinosa says. “The injection technique is currently being explored for delivery of a wide variety of bio-agents, including DNA, viruses and other therapeutically relevant materials.”
Nanodiamonds have also proven effective in seeding the growth of diamond thin films. These diamond films have exciting applications in next-generation nanoelectronics. Here again, the ability to pattern nanodiamonds with sub-100-nanometer resolution provides inroads to realizing these devices on a mass scale. The resolution in nanodiamond patterning demonstrated by the Nanofountain Probe represents an improvement of three orders of magnitude over other reported direct-write schemes of nanodiamond patterning.
The work was supported by the National Science Foundation, the National Institutes of Health, the V Foundation for Cancer Research and the Wallace H. Coulter Foundation.
In addition to Espinosa and Ho, other authors of the paper, entitled “Nanofountain Probe-based High-resolution Patterning and Single-cell Injection of Functionalized Nanodiamonds,” are Owen Loh, Robert Lam, Mark Chen, Nicolaie Moldovan and Houjin Huang of Northwestern University.
>http://www.nanotechwire.com/news.asp?nid=7939
Showing posts with label NanoMedicine. Show all posts
Showing posts with label NanoMedicine. Show all posts
Monday, June 15, 2009
Drug Delivery
NanoVentures Australia
Unveils Novel Pulmonary Drug Delivery Technology
NVA’s predecessor, Nanotechnology Victoria Ltd (”NanoVic”) invested nearly $500,000 with Monash University’s Micro NanoPhysics Research Laboratory to develop and demonstrate a novel mechanism for generation of liquid aerosol drugs. The proprietary SAW (Surface Acoustic Wave) generated mechanism allows fluids to be atomised as precisely controlled droplets, making them ideal for a new generation of inhaler devices. These inhalers are likely to be very low cost, as they require very few moving parts.
Further, the SAW technology means that drugs like insulin can be delivered in fluid droplet form from an inhaler. Previous attempts to deliver insulin from an inhaler have used dry powders, which are more difficult to control, and may cause new issues for certain groups of patients.
Last month, NVA and Monash University filed for the protection of new intellectual property around their proprietary pulmonary drug delivery device. The parties hold the Australian provisional patent application 2009902063 Microfluidics apparatus for the atomisation of a liquid. In particular the team has demonstrated in vitro results with maintenance of insulin structure and function after aerosolisation, and over 70% delivery to the lungs using the test protein insulin.
There has been growing interest in the potential for the systematic delivery of drugs and therapeutic agents (e.g. peptides and proteins) via inhalation. Pulmonary drug delivery is an attractive option compared to oral administration or other invasive delivery techniques, and is particularly suited to a number of frequent-application drugs. The surface acoustic atomisation technology developed by Monash University provides for the controlled generation of aerosol particles, and is ideal for drug delivery to the deep regions of the lungs.
NVA has exclusive rights to the exploitation of the technology for potential applications in the administration of insulin and erythropoietin, as well as for the treatment of Cystic Fibrosis and Multiple Sclerosis.
The delivery device R&D program, led by Associate Professor James Friend at the Monash University Micro NanoPhysics Research Laboratory, commenced in January 2007 and is due for completion in October 2009. Dr Friend is internationally known for his leadership in the application of nanotechnology to medical devices.
NVA commercialises nanotechnologies developed by Nanotechnology Victoria Ltd (”NanoVic”), the Victorian Government funded nanotechnology accelerator which operated from 2002 to 2009. NVA has a portfolio of other technologies being positioned for commercial development, in medical therapeutics, diagnostics, advanced materials and water analysis and purification. NVA commercialises nanotechnologies developed by Nanotechnology Victoria Ltd (”NanoVic”), the Victorian Government funded nanotechnology accelerator which operated from 2002 to 2009.
>http://www.nanotechwire.com/news.asp?nid=8000
Unveils Novel Pulmonary Drug Delivery Technology
NVA’s predecessor, Nanotechnology Victoria Ltd (”NanoVic”) invested nearly $500,000 with Monash University’s Micro NanoPhysics Research Laboratory to develop and demonstrate a novel mechanism for generation of liquid aerosol drugs. The proprietary SAW (Surface Acoustic Wave) generated mechanism allows fluids to be atomised as precisely controlled droplets, making them ideal for a new generation of inhaler devices. These inhalers are likely to be very low cost, as they require very few moving parts.
Further, the SAW technology means that drugs like insulin can be delivered in fluid droplet form from an inhaler. Previous attempts to deliver insulin from an inhaler have used dry powders, which are more difficult to control, and may cause new issues for certain groups of patients.
Last month, NVA and Monash University filed for the protection of new intellectual property around their proprietary pulmonary drug delivery device. The parties hold the Australian provisional patent application 2009902063 Microfluidics apparatus for the atomisation of a liquid. In particular the team has demonstrated in vitro results with maintenance of insulin structure and function after aerosolisation, and over 70% delivery to the lungs using the test protein insulin.
There has been growing interest in the potential for the systematic delivery of drugs and therapeutic agents (e.g. peptides and proteins) via inhalation. Pulmonary drug delivery is an attractive option compared to oral administration or other invasive delivery techniques, and is particularly suited to a number of frequent-application drugs. The surface acoustic atomisation technology developed by Monash University provides for the controlled generation of aerosol particles, and is ideal for drug delivery to the deep regions of the lungs.
NVA has exclusive rights to the exploitation of the technology for potential applications in the administration of insulin and erythropoietin, as well as for the treatment of Cystic Fibrosis and Multiple Sclerosis.
The delivery device R&D program, led by Associate Professor James Friend at the Monash University Micro NanoPhysics Research Laboratory, commenced in January 2007 and is due for completion in October 2009. Dr Friend is internationally known for his leadership in the application of nanotechnology to medical devices.
NVA commercialises nanotechnologies developed by Nanotechnology Victoria Ltd (”NanoVic”), the Victorian Government funded nanotechnology accelerator which operated from 2002 to 2009. NVA has a portfolio of other technologies being positioned for commercial development, in medical therapeutics, diagnostics, advanced materials and water analysis and purification. NVA commercialises nanotechnologies developed by Nanotechnology Victoria Ltd (”NanoVic”), the Victorian Government funded nanotechnology accelerator which operated from 2002 to 2009.
>http://www.nanotechwire.com/news.asp?nid=8000
Nanotechnology
UB Scientists Develop Novel Nanotechnology
Method to Stimulate Growth of New Neurons in Adult Brain
University at Buffalo researchers have identified a new mechanism that plays a central role in adult brain stem cell development and prompts brain stem cells to differentiate into neurons.
Their discovery, known as Integrative FGFR1 Signaling (INFS), has fundamentally challenged the prevailing ideas of how signals are processed in cells during neuronal development.
The INFS mechanism is considered capable of repopulating degenerated brain areas, raising possibilities for new treatments for Parkinson’s disease, Alzheimer’s disease and other neurodegenerative disorders, and may be a promising anti-cancer therapy.
Michal Stachowiak, Ph.D., director of the Molecular and Structural Neurobiology and Gene Therapy Program at UB, lead the research team that discovered INFS.
Results of the research appear in a recent issue of Integrative Biology at http://xlink.rsc.org/?doi=B902617G.
The approach uses gene engineering and nanoparticles for gene delivery to activate the INFS mechanism directly and promote neuronal development. The INFS-targeting gene can prompt these stem cells to differentiate into neurons.
Stachowiak, UB associate professor of pathology and anatomical sciences in the UB School of Medicine and Biomedical Sciences, said the research team set out to see if it is possible to generate a wave of new neurons from stem cells and direct them to the affected areas using a mouse model.
“In this way, targeting the INFS potentially could be used to cure certain brain diseases, particularly in the case of a stroke or injuries that happen as a single episode and are not continuously attacking the brain,” he said.
“This study provides proof of concept for a novel approach to the treatment of neuronal loss by means of therapeutic gene transfer. This is a particularly attractive alternative to viral-mediated gene transfer.
“The health risks associated with using viruses to carry genes in this type of gene transfer have led to the search for safer means of gene delivery,” noted Stachowiak. “Nanotechnology offers an unprecedented advantage in enhancing the efficacy of non-viral gene delivery.”
Stachowiak and his wife, Ewa K. Stachowiak, Ph.D., research assistant professor of pathology and anatomical sciences, along with their postdoctoral fellows and graduate students, have spent more than 15 years studying the mechanisms controlling natural neurogenesis, the creation of new neurons.
Brain injuries, stroke and progressive chronic diseases such as Parkinson’s or Alzheimer’s disease result in an extensive loss of neurons, accompanied by functional deterioration in the affected brain tissue. Such neurodegenerative diseases are a major health concern, given the rising aging population worldwide.
In addition, neurodevelopmental disorders, such as autism and schizophrenia, diminish the production of neurons and disrupt the brain’s cellular structure.
“Manipulation of pre-existing adult stem cells to repopulate diseased areas of the brain holds the key towards the treatment of these neurodegenerative and, possibly, neurodevelopmental disorders,” said Michal Stachowiak.
“However, after birth, the ability of the brain’s stem cells to form the necessary new neurons normally is greatly diminished, and the mechanisms controlling natural neurogenesis are not well understood.”
The neurogenic potential of targeting INFS was described initially in cultured stem cells in vitro by the Stachowiak team. Following these initial studies, together with a team of UB chemists that included Indrajit Roy, Ph.D., Dhruba Bharali, Ph.D., and Paras N. Prasad, Ph.D., Stachowiak’s group investigated the use of organically modified silica nanoparticles as gene delivery vehicles into the stem cells of the brain in vivo.
Prasad is executive director of the UB Institute for Lasers, Photonics and Biophotonics and SUNY Distinguished Professor in the departments of Chemistry, Physics, Electrical Engineering and Medicine. Roy is an assistant research professor in the institute; Bharali was a research associate.
Injae Shin, Ph.D., an expert in genetics at Yonsei University, Seoul, Korea, in an online article on the Chemical Biology Web site, called the work “exciting.” He noted that it has the potential to treat neurological diseases, but pointed out the need for further development of gene delivery methods for the treatment of neuronal loss.
Stachowiak and colleagues currently are working on such approaches.
“Targeting the INFS mechanisms by small molecules could potentially replace the need for gene transfers and create a classical drug therapy for the neuronal loss,” said Ewa Stachowiak. “Now that we know the mechanism, we can search effectively for the means to control it.”
>http://www.nanotechwire.com/news.asp?nid=7956
Method to Stimulate Growth of New Neurons in Adult Brain
University at Buffalo researchers have identified a new mechanism that plays a central role in adult brain stem cell development and prompts brain stem cells to differentiate into neurons.
Their discovery, known as Integrative FGFR1 Signaling (INFS), has fundamentally challenged the prevailing ideas of how signals are processed in cells during neuronal development.
The INFS mechanism is considered capable of repopulating degenerated brain areas, raising possibilities for new treatments for Parkinson’s disease, Alzheimer’s disease and other neurodegenerative disorders, and may be a promising anti-cancer therapy.
Michal Stachowiak, Ph.D., director of the Molecular and Structural Neurobiology and Gene Therapy Program at UB, lead the research team that discovered INFS.
Results of the research appear in a recent issue of Integrative Biology at http://xlink.rsc.org/?doi=B902617G.
The approach uses gene engineering and nanoparticles for gene delivery to activate the INFS mechanism directly and promote neuronal development. The INFS-targeting gene can prompt these stem cells to differentiate into neurons.
Stachowiak, UB associate professor of pathology and anatomical sciences in the UB School of Medicine and Biomedical Sciences, said the research team set out to see if it is possible to generate a wave of new neurons from stem cells and direct them to the affected areas using a mouse model.
“In this way, targeting the INFS potentially could be used to cure certain brain diseases, particularly in the case of a stroke or injuries that happen as a single episode and are not continuously attacking the brain,” he said.
“This study provides proof of concept for a novel approach to the treatment of neuronal loss by means of therapeutic gene transfer. This is a particularly attractive alternative to viral-mediated gene transfer.
“The health risks associated with using viruses to carry genes in this type of gene transfer have led to the search for safer means of gene delivery,” noted Stachowiak. “Nanotechnology offers an unprecedented advantage in enhancing the efficacy of non-viral gene delivery.”
Stachowiak and his wife, Ewa K. Stachowiak, Ph.D., research assistant professor of pathology and anatomical sciences, along with their postdoctoral fellows and graduate students, have spent more than 15 years studying the mechanisms controlling natural neurogenesis, the creation of new neurons.
Brain injuries, stroke and progressive chronic diseases such as Parkinson’s or Alzheimer’s disease result in an extensive loss of neurons, accompanied by functional deterioration in the affected brain tissue. Such neurodegenerative diseases are a major health concern, given the rising aging population worldwide.
In addition, neurodevelopmental disorders, such as autism and schizophrenia, diminish the production of neurons and disrupt the brain’s cellular structure.
“Manipulation of pre-existing adult stem cells to repopulate diseased areas of the brain holds the key towards the treatment of these neurodegenerative and, possibly, neurodevelopmental disorders,” said Michal Stachowiak.
“However, after birth, the ability of the brain’s stem cells to form the necessary new neurons normally is greatly diminished, and the mechanisms controlling natural neurogenesis are not well understood.”
The neurogenic potential of targeting INFS was described initially in cultured stem cells in vitro by the Stachowiak team. Following these initial studies, together with a team of UB chemists that included Indrajit Roy, Ph.D., Dhruba Bharali, Ph.D., and Paras N. Prasad, Ph.D., Stachowiak’s group investigated the use of organically modified silica nanoparticles as gene delivery vehicles into the stem cells of the brain in vivo.
Prasad is executive director of the UB Institute for Lasers, Photonics and Biophotonics and SUNY Distinguished Professor in the departments of Chemistry, Physics, Electrical Engineering and Medicine. Roy is an assistant research professor in the institute; Bharali was a research associate.
Injae Shin, Ph.D., an expert in genetics at Yonsei University, Seoul, Korea, in an online article on the Chemical Biology Web site, called the work “exciting.” He noted that it has the potential to treat neurological diseases, but pointed out the need for further development of gene delivery methods for the treatment of neuronal loss.
Stachowiak and colleagues currently are working on such approaches.
“Targeting the INFS mechanisms by small molecules could potentially replace the need for gene transfers and create a classical drug therapy for the neuronal loss,” said Ewa Stachowiak. “Now that we know the mechanism, we can search effectively for the means to control it.”
>http://www.nanotechwire.com/news.asp?nid=7956
Capsules encapsulated
Drug Deliver With Nanotechnology:
Capsules Encapsulated
When cells cannot carry out the tasks required of them by our bodies, the result is disease. Nanobiotechnology researchers are looking for ways to allow synthetic systems take over simple cellular activities when they are absent from the cell. This requires transport systems that can encapsulate medications and other substances and release them in a controlled fashion at the right moment.
The transporter must be able to interact with the surroundings in order to receive the signal to unload its cargo. A team led by Frank Caruso at the University of Melbourne has now developed a microcontainer that can hold thousands of individual "carrier units"—a "capsosome". These are polymer capsules in which liposomes have been embedded to form subcompartments.
Currently, the primary type of nanotransporter used for drugs is the capsule: Polymer capsules form stable containers that are semipermeable, which allows for communication with the surrounding medium. However, these are not suitable for the transport of small molecules because they can escape. Liposomes are good at protecting small drug molecules; however, they are often unstable and impermeable to substances from the environment. The Australian researchers have now combined the advantages of both systems in their capsosomes.
Capsosomes are produced by several steps. First, a layer of polymer is deposited onto small silica spheres. This polymer contains building blocks modified with cholesterol. Liposomes that have been loaded with an enzyme can be securely anchored to the cholesterol units and thus attached to the polymer film. Subsequently, more polymer layers are added and then cross-linked by disulfide bridges into a gel by means of a specially developed, very gentle cross-linking reaction. In the final step, the silica core is etched away without damaging the sensitive cargo.
Experiments with an enzyme as model cargo demonstrated that the liposomes remain intact and the cargo does not escape. Addition of a detergent releases the enzyme in a functional state. By means of the enzymatic reaction, which causes a color change of the solution, it was possible to determine the number of liposome compartments to be about 8000 per polymer capsule.
"Because the capsosomes are biodegradable and nontoxic", says Brigitte Staedler, a senior researcher in the group, "they would also be suitable for use as resorbable synthetic cell organelles and for the transport of drugs." In addition, the scientists are planning to encapsulate liposomes filled with different enzymes together and to equip them with specific "receivers" which would allow the individual cargo to be released in a targeted fashion. This would make it possible to use enzymatic reaction cascades for catalytic reaction processes.
Frank Caruso. A Microreactor with Thousands of Subcompartments: Enzyme-Loaded Liposomes within Polymer Capsules. Angewandte Chemie International
Edition, 2009, 48, No. 24, 4359-4362 DOI: 10.1002/anie.200900386
>http://www.nanotechwire.com/news.asp?nid=7944
Capsules Encapsulated
When cells cannot carry out the tasks required of them by our bodies, the result is disease. Nanobiotechnology researchers are looking for ways to allow synthetic systems take over simple cellular activities when they are absent from the cell. This requires transport systems that can encapsulate medications and other substances and release them in a controlled fashion at the right moment.
The transporter must be able to interact with the surroundings in order to receive the signal to unload its cargo. A team led by Frank Caruso at the University of Melbourne has now developed a microcontainer that can hold thousands of individual "carrier units"—a "capsosome". These are polymer capsules in which liposomes have been embedded to form subcompartments.
Currently, the primary type of nanotransporter used for drugs is the capsule: Polymer capsules form stable containers that are semipermeable, which allows for communication with the surrounding medium. However, these are not suitable for the transport of small molecules because they can escape. Liposomes are good at protecting small drug molecules; however, they are often unstable and impermeable to substances from the environment. The Australian researchers have now combined the advantages of both systems in their capsosomes.
Capsosomes are produced by several steps. First, a layer of polymer is deposited onto small silica spheres. This polymer contains building blocks modified with cholesterol. Liposomes that have been loaded with an enzyme can be securely anchored to the cholesterol units and thus attached to the polymer film. Subsequently, more polymer layers are added and then cross-linked by disulfide bridges into a gel by means of a specially developed, very gentle cross-linking reaction. In the final step, the silica core is etched away without damaging the sensitive cargo.
Experiments with an enzyme as model cargo demonstrated that the liposomes remain intact and the cargo does not escape. Addition of a detergent releases the enzyme in a functional state. By means of the enzymatic reaction, which causes a color change of the solution, it was possible to determine the number of liposome compartments to be about 8000 per polymer capsule.
"Because the capsosomes are biodegradable and nontoxic", says Brigitte Staedler, a senior researcher in the group, "they would also be suitable for use as resorbable synthetic cell organelles and for the transport of drugs." In addition, the scientists are planning to encapsulate liposomes filled with different enzymes together and to equip them with specific "receivers" which would allow the individual cargo to be released in a targeted fashion. This would make it possible to use enzymatic reaction cascades for catalytic reaction processes.
Frank Caruso. A Microreactor with Thousands of Subcompartments: Enzyme-Loaded Liposomes within Polymer Capsules. Angewandte Chemie International
Edition, 2009, 48, No. 24, 4359-4362 DOI: 10.1002/anie.200900386
>http://www.nanotechwire.com/news.asp?nid=7944
Dead or alive
Nanotechnology technique tells the difference
(Nanowerk Spotlight)
A major concern in microbiology is to determine whether a bacterium is dead or alive. This crucial question has major consequences in food industry, water supply or health care. While culture-based tests can determine whether bacteria can proliferate and form colonies, these tests are time-consuming and work poorly with certain slow-growing or non-culturable bacteria. They are not suitable for applications where real-time results are needed, e.g. in industrial manufacturing or food processing. A team of scientists in France has now discovered that living and dead cells can be discriminated with a nanotechnology technique on the basis of their cell wall nanomechanical properties. This finding is totally new and has been made possible thanks to an interdisciplinary approach which mixes physics, biology and chemistry. This work is a key stone in the understanding of bacterial cell wall behavior. "We have developed a method to probe the mechanical properties of living and dead bacteria via atomic force microscope (AFM) indentation experimentations," Aline Cerf tells Nanowerk. ". Indeed, we provide a new way to probe bacterial cell viability based on cell wall nanomechanical properties, independently from cell ability to grow on a medium or to be penetrated by a fluorescent dye." Cerf, a PhD student in the NanoBioSystems group at LAAS-CNRS, is first author of a recent paper in Langmuir ("Nanomechanical Properties of Dead or Alive Single-Patterned Bacteria") where she and collaborators from LAAS-CNRS describe their findings. "We wanted to explore the modifications that could occur in the nanomechanical properties of a single E. coli bacterium, while it is alive and while it is dead," says Etienne Dague, a researcher in the NanoBioSystems group. "To reach this goal, it has been of first importance to immobilize the living bacteria in an aqueous environment to avoid any cell wall modifications due to a drying step." Thus, in developing a technique to probe the mechanical properties of bacteria via AFM indentation experiments, the French team also came up with an immobilization method for bacteria that doesn't require a chemical fixation.
The researchers set up a fast and simple procedure – based on a conventional microcontact printing and a simple incubation technique to generate functionalized patterns so as to induce local bacteria deposition – that allowed them to produce reliable chemical patterns exhibiting different surface properties to induce selective adsorption of individual bacteria in liquid media at registered positions. "We have evidenced a selective adsorption of bacteria on these local chemical patterns, producing highly ordered arrays of single living bacteria with a success rate close to 100%," says Cerf. The team then used this controlled immobilization method to study the mechanical properties of dead or alive bacterial cell in aqueous environment. Using force spectroscopy before and after heating , they measured the Young moduli of the same cell. The cells with a damaged membrane (after heating) present a Young modulus twice as high (6.1 ? 1.5 MPa versus 3.0 ? 0.6 MPa) as that of healthy bacteria. At the same time it has been impossible to evidence a difference between the AFM images of the living and the dead cell. "We have shown that we are capable of engineering large areas with patterns of single bacteria and this will be of major interest for future applications," says Dague. "Indeed, thanks to a periodic arrangement of cells, the process consisting in measuring the nanomechanical properties of cells could possibly be automated and a tool to count live or dead bacteria could be designed."
The researchers set up a fast and simple procedure – based on a conventional microcontact printing and a simple incubation technique to generate functionalized patterns so as to induce local bacteria deposition – that allowed them to produce reliable chemical patterns exhibiting different surface properties to induce selective adsorption of individual bacteria in liquid media at registered positions. "We have evidenced a selective adsorption of bacteria on these local chemical patterns, producing highly ordered arrays of single living bacteria with a success rate close to 100%," says Cerf. The team then used this controlled immobilization method to study the mechanical properties of dead or alive bacterial cell in aqueous environment. Using force spectroscopy before and after heating , they measured the Young moduli of the same cell. The cells with a damaged membrane (after heating) present a Young modulus twice as high (6.1 ? 1.5 MPa versus 3.0 ? 0.6 MPa) as that of healthy bacteria. At the same time it has been impossible to evidence a difference between the AFM images of the living and the dead cell. "We have shown that we are capable of engineering large areas with patterns of single bacteria and this will be of major interest for future applications," says Dague. "Indeed, thanks to a periodic arrangement of cells, the process consisting in measuring the nanomechanical properties of cells could possibly be automated and a tool to count live or dead bacteria could be designed."
By Michael Berger. Copyright 2009 Nanowerk LLC >http://www.nanowerk.com/spotlight/spotid=10816.php
Virus Battery
MIT researchers make virus battery
WASHINGTON, April 2 (Xinhua)
For the first time, MIT researchers have shown they can genetically engineer viruses to build both the positively and negatively charged ends of a lithium-ion battery, according to a study released on Thursday in the online edition of journal Science.
The new virus-produced batteries have the same energy capacity and power performance as state-of-the-art rechargeable batteries being considered to power plug-in hybrid cars, and they could also be used to power a range of personal electronic devices, said Angela Belcher, the MIT materials scientist who led the research team.
The new batteries could be manufactured with a cheap and environmentally benign process: The synthesis takes place at and below room temperature and requires no harmful organic solvents, and the materials that go into the battery are non-toxic.
In a traditional lithium-ion battery, lithium ions flow between a negatively charged anode, usually graphite, and the positively charged cathode, usually cobalt oxide or lithium iron phosphate. Three years ago, an MIT team led by Belcher reported that it had engineered viruses that could build an anode by coating themselves with cobalt oxide and gold and self-assembling to form a nanowire.
In the latest work, the team focused on building a highly powerful cathode to pair up with the anode, said Belcher, the Germeshausen Professor of Materials Science and Engineering and Biological Engineering in MIT. Cathodes are more difficult to build than anodes because they must be highly conducting to be a fast electrode. However, most candidate materials for cathodes are highly insulating (non-conductive).
To achieve that, the researchers, including MIT Professor Gerbrand Ceder of materials science and Associate Professor Michael Strano of chemical engineering, genetically engineered viruses that first coat themselves with iron phosphate, then grab hold of carbon nanotubes to create a network of highly conductive material.
Because the viruses recognize and bind specifically to certain materials (carbon nanotubes in this case), each iron phosphate nanowire can be electrically "wired" to conducting carbon nanotubenetworks. Electrons can travel along the carbon nanotube networks, percolating throughout the electrodes to the iron phosphate and transferring energy in a very short time.
The viruses are a common bacteriophage, which infect bacteria but are harmless to humans.
The team found that incorporating carbon nanotubes increases the cathode's conductivity without adding too much weight to the battery. In lab tests, batteries with the new cathode material could be charged and discharged at least 100 times without losing any capacitance. That is fewer charge cycles than currently available lithium-ion batteries, but "we expect them to be able to go much longer," Belcher said.
The prototype is packaged as a typical coin cell battery, but the technology allows for the assembly of very lightweight, flexible and conformable batteries that can take the shape of their container.
Last week, MIT President Susan Hockfield took the prototype battery to a press briefing at the White House where she and U.S. President Barack Obama spoke about the need for federal funding to advance new clean-energy technologies.
Now that the researchers have demonstrated they can wire virus batteries at the nanoscale, they intend to pursue even better batteries using materials with higher voltage and capacitance, such as manganese phosphate and nickel phosphate, said Belcher. Once that next generation is ready, the technology could go into commercial production, she said.
source: > www.chinaview.cn
Editor: Mu Xuequan
WASHINGTON, April 2 (Xinhua)
For the first time, MIT researchers have shown they can genetically engineer viruses to build both the positively and negatively charged ends of a lithium-ion battery, according to a study released on Thursday in the online edition of journal Science.
The new virus-produced batteries have the same energy capacity and power performance as state-of-the-art rechargeable batteries being considered to power plug-in hybrid cars, and they could also be used to power a range of personal electronic devices, said Angela Belcher, the MIT materials scientist who led the research team.
The new batteries could be manufactured with a cheap and environmentally benign process: The synthesis takes place at and below room temperature and requires no harmful organic solvents, and the materials that go into the battery are non-toxic.
In a traditional lithium-ion battery, lithium ions flow between a negatively charged anode, usually graphite, and the positively charged cathode, usually cobalt oxide or lithium iron phosphate. Three years ago, an MIT team led by Belcher reported that it had engineered viruses that could build an anode by coating themselves with cobalt oxide and gold and self-assembling to form a nanowire.
In the latest work, the team focused on building a highly powerful cathode to pair up with the anode, said Belcher, the Germeshausen Professor of Materials Science and Engineering and Biological Engineering in MIT. Cathodes are more difficult to build than anodes because they must be highly conducting to be a fast electrode. However, most candidate materials for cathodes are highly insulating (non-conductive).
To achieve that, the researchers, including MIT Professor Gerbrand Ceder of materials science and Associate Professor Michael Strano of chemical engineering, genetically engineered viruses that first coat themselves with iron phosphate, then grab hold of carbon nanotubes to create a network of highly conductive material.
Because the viruses recognize and bind specifically to certain materials (carbon nanotubes in this case), each iron phosphate nanowire can be electrically "wired" to conducting carbon nanotubenetworks. Electrons can travel along the carbon nanotube networks, percolating throughout the electrodes to the iron phosphate and transferring energy in a very short time.
The viruses are a common bacteriophage, which infect bacteria but are harmless to humans.
The team found that incorporating carbon nanotubes increases the cathode's conductivity without adding too much weight to the battery. In lab tests, batteries with the new cathode material could be charged and discharged at least 100 times without losing any capacitance. That is fewer charge cycles than currently available lithium-ion batteries, but "we expect them to be able to go much longer," Belcher said.
The prototype is packaged as a typical coin cell battery, but the technology allows for the assembly of very lightweight, flexible and conformable batteries that can take the shape of their container.
Last week, MIT President Susan Hockfield took the prototype battery to a press briefing at the White House where she and U.S. President Barack Obama spoke about the need for federal funding to advance new clean-energy technologies.
Now that the researchers have demonstrated they can wire virus batteries at the nanoscale, they intend to pursue even better batteries using materials with higher voltage and capacitance, such as manganese phosphate and nickel phosphate, said Belcher. Once that next generation is ready, the technology could go into commercial production, she said.
source: > www.chinaview.cn
Editor: Mu Xuequan
Thursday, June 11, 2009
Future Medicine
The photonic nanomedicine revolution:
Let the human side of nanotechnology emerge
Naomi J Halas
Department of Electrical & Computer Engineering & the Laboratory for Nanophotonics,
Rice University, 6100 Main St., Houston, TX 77005-1892, USA. halas@rice.edu
Nanoparticle-based photothermal ablation is showing extraordinary promise as an unusually effective and potentially revolutionary cancer therapy. This approach uses light at near-infrared wavelengths that pass through tissue, in combination with gold-based nanoparticles specifically engineered to absorb that light and convert it to heat. The light-absorbing nanoparticles serve as highly localized heat sources that destroy cells in their immediate vicinity by hyperthermia [4]. This method has been shown to be highly effective in extensive animal studies, with tumor remission rates above 90%. Extensive toxicity studies have been performed on nanoshells, the nanoparticles most utilized to date in these studies, and this is being followed by similar studies on other types of noble metal nanoparticles that are also promising candidates for this therapeutic modality. The US FDA has recently granted approval for initial human trials of this therapy for head and neck cancer. Given the extraordinary promise of these potentially revolutionary therapeutic nanodevices and their impending availability, research into nanoparticle-based therapeutics is beginning to move into the next critical phase: the development of nanoparticle-assisted therapeutic practices specifically for clinical use.
One of the most extraordinary aspects of nanoparticle-assisted photothermal therapy for tumor remission is that it is drug free: cell death is induced by the localized heat generated when the nanoparticles absorb near-infrared light. This is an exceedingly important aspect: with heat as the source of cell death, this approach is independent of the specifics of the immune systems of various animals on which it may be tested. This also means that with this therapeutic approach, the nanoparticles can be classified as a device, rather than a drug. They are nanoscale lenses, delivering highly focused light to cancer cells or within tumors much like a lens that captures sunlight delivers enough heat to a leaf to enable it to burst into flames. However, in the case of nanoparticle-based photothermal therapy, the heat required to induce cell death is only approximately 15–20? above physiological temperatures. Because the nanoparticles are devices and not drugs, operating only on heat and light and not interacting chemically with living systems, this therapy, and other variants of this approach, may be available for patients and practitioners in just a few years.
For cancer, this nanoparticle-based strategy will ultimately allow the clinician to remove localized tumors with a simple, minimally invasive, nonsurgical procedure performed, for example, with a portable laser in an outpatient clinic instead of a surgical suite. This could fundamentally revolutionize the treatment of virtually all soft-tissue cancers, transforming this feared, life-threatening disease to an actively managed illness that can be treated and contained prophylactically.
While early detection and treatment of localized, noninvasive tumors is ideal, in reality it is not the typical diagnostic scenario. In any given year, invasive carcinoma diagnoses far outnumber the diagnosed cases of localized cancer. While nanoparticle-based photothermal therapy appears to be highly promising for the removal of localized tumors, an important and immediate challenge is to develop strategies to address more advanced stages of cancer with this powerful new modality. The proliferation of cancer to the lymph nodes directly adjacent to the primary tumor is a key diagnostic for cancer clinicians, and determines the course of treatment. In conventional surgery, these adjacent lymph nodes are typically removed along with the primary tumor. Recent advances in the development of strongly enhanced fluorescent markers for deep-tissue imaging may make resolution at the limit of a few cells possible. Targeted imaging of cancer in lymph nodes, to quantify the proliferation of cancer beyond carcinoma in situ, could be combined with photothermal destruction of targeted cancer cells using nanoparticle-based probes. This would provide a method for removing the cancer cells in the lymph nodes while preserving, largely intact, the lymphatic system of the cancer patient. As markers become available this general approach should be extendable to additional strategies for the treatment of metastatic disease.
The centers of solid tumors are frequently observed to be largely necrotic, resulting from prolonged hypoxia: insufficient availability of oxygen and glucose to meet the metabolic demands of the malignant cells. Because of the decreased blood flow in these tumor regions, they are inaccessible by, and therefore highly resistant to, conventional chemotherapies. One possible scenario for the progression of cancer to its latter, highly fatal stages is that cells surviving in these inaccessible hypoxic regions may themselves be the source of subsequent local recurrence and distant metastasis. One of the body’s responses to the presence of a malignant neoplasm is to recruit peripheral blood monocytes into the tumor, which then differentiate into macrophages. These cells have been shown to promote metastatic disease. One potentially promising scenario is to induce uptake of nanoshells into monocytes, which are then recruited into the hypoxic regions of tumors: the presence of the nanoshells would then permit photothermal destruction of the necrotic region. This type of approach may provide a critical new strategy for thwarting tumor metastasis.
An exciting new use of nanoparticle-assisted photothermal therapy is in delivery methods for gene therapy. It is widely recognized that gene-based therapies hold extraordinary therapeutic promise for cancer: many genetic markers have been discovered, and numerous DNA-based therapeutics have been proposed for the targeting of pathogenic genes for various cancers. Genetic vaccines have also been suggested for certain forms of cancer now believed to have a hereditary basis, such as the 42–57% of prostate cancer cases that correlate with inherited genetic factors. However, while the discovery of gene targets and the development of gene-based therapies at the molecular level has been pursued aggressively for more than 15 years, the transition of these therapies from the research laboratory to the clinic is at a virtual impasse and fraught with severe challenges. Unprotected gene therapy drugs (DNA- or RNA-based) introduced into the bloodstream are rapidly broken down, preventing their diffusion to the region of disease. Viruses, the initial carrier of choice in most gene therapy research, present a variety of potential problems to the patient – toxicity, immune and inflammatory responses, and gene control and targeting issues. The first clinical gene therapy studies utilizing a viral delivery vector resulted in patient death, and had to be terminated in their initial stage. There is a clear critical need for nonviral delivery vectors for gene therapy for this field to advance towards its many clinical applications. Nanoparticle–biomolecule light-actuated complexes are being developed and tested with clinically relevant genetic markers. For example, by combining gold nanoparticles with specific oligonucleotides, the nanoparticle complex can serve as a nonviral gene-delivery vector, where incident light can trigger the release of the nucleotide once the complex has been taken up by cells. Initial release data in cell culture studies show that this approach has outstanding promise for gene delivery. Light-triggered nucleotide release from these nanoparticle–molecule complexes makes them particularly well suited for the localized administration of gene therapy drugs into the tissue or organ of interest.
In conclusion, nanoparticle-assisted, photothermal therapeutic strategies have the capability of providing revolutionary tools in many battles against human disease, with the clear potential for highly effective therapy for cancer and other diseases. Moreover, this approach is unparalleled in its level of noninvasiveness and in its low, essentially nonexistent toxicity. The long-term impact of the development of these new treatment methods will be to change the way we treat cancer. This approach may also provide effective new strategies for treatments of other, lesser known and less-studied diseases such as autoimmune disorders, where few or no treatment options currently exist. In addition to increased efficacy, an extraordinary advantage of nanoparticle-assisted photothermal therapy is that essentially no, or minimal, side effects are expected. Replacing current chemotherapy treatments, with their high level of systemic toxicity and deleterious side effects, with this benign therapeutic approach will greatly increase the quality of life for cancer patients and their families.
Financial & competing interests disclosure The author is the inventor of nanoshells and pioneered nanoparticle-based photothermal therapies along with her collaborators at Rice University (TX, USA), J West and R Drezek. She is the co-founder of Nanospectra Biosciences, Inc. (http://www.nanospectra.com/), a Houston-based company dedicated to the translation of this therapeutic approach into clinical practice. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Source >http://www.futuremedicine.com/doi/full/10.2217/nnm.09.26
Let the human side of nanotechnology emerge
Naomi J Halas
Department of Electrical & Computer Engineering & the Laboratory for Nanophotonics,
Rice University, 6100 Main St., Houston, TX 77005-1892, USA. halas@rice.edu
Nanoparticle-based photothermal ablation is showing extraordinary promise as an unusually effective and potentially revolutionary cancer therapy. This approach uses light at near-infrared wavelengths that pass through tissue, in combination with gold-based nanoparticles specifically engineered to absorb that light and convert it to heat. The light-absorbing nanoparticles serve as highly localized heat sources that destroy cells in their immediate vicinity by hyperthermia [4]. This method has been shown to be highly effective in extensive animal studies, with tumor remission rates above 90%. Extensive toxicity studies have been performed on nanoshells, the nanoparticles most utilized to date in these studies, and this is being followed by similar studies on other types of noble metal nanoparticles that are also promising candidates for this therapeutic modality. The US FDA has recently granted approval for initial human trials of this therapy for head and neck cancer. Given the extraordinary promise of these potentially revolutionary therapeutic nanodevices and their impending availability, research into nanoparticle-based therapeutics is beginning to move into the next critical phase: the development of nanoparticle-assisted therapeutic practices specifically for clinical use.
One of the most extraordinary aspects of nanoparticle-assisted photothermal therapy for tumor remission is that it is drug free: cell death is induced by the localized heat generated when the nanoparticles absorb near-infrared light. This is an exceedingly important aspect: with heat as the source of cell death, this approach is independent of the specifics of the immune systems of various animals on which it may be tested. This also means that with this therapeutic approach, the nanoparticles can be classified as a device, rather than a drug. They are nanoscale lenses, delivering highly focused light to cancer cells or within tumors much like a lens that captures sunlight delivers enough heat to a leaf to enable it to burst into flames. However, in the case of nanoparticle-based photothermal therapy, the heat required to induce cell death is only approximately 15–20? above physiological temperatures. Because the nanoparticles are devices and not drugs, operating only on heat and light and not interacting chemically with living systems, this therapy, and other variants of this approach, may be available for patients and practitioners in just a few years.
For cancer, this nanoparticle-based strategy will ultimately allow the clinician to remove localized tumors with a simple, minimally invasive, nonsurgical procedure performed, for example, with a portable laser in an outpatient clinic instead of a surgical suite. This could fundamentally revolutionize the treatment of virtually all soft-tissue cancers, transforming this feared, life-threatening disease to an actively managed illness that can be treated and contained prophylactically.
While early detection and treatment of localized, noninvasive tumors is ideal, in reality it is not the typical diagnostic scenario. In any given year, invasive carcinoma diagnoses far outnumber the diagnosed cases of localized cancer. While nanoparticle-based photothermal therapy appears to be highly promising for the removal of localized tumors, an important and immediate challenge is to develop strategies to address more advanced stages of cancer with this powerful new modality. The proliferation of cancer to the lymph nodes directly adjacent to the primary tumor is a key diagnostic for cancer clinicians, and determines the course of treatment. In conventional surgery, these adjacent lymph nodes are typically removed along with the primary tumor. Recent advances in the development of strongly enhanced fluorescent markers for deep-tissue imaging may make resolution at the limit of a few cells possible. Targeted imaging of cancer in lymph nodes, to quantify the proliferation of cancer beyond carcinoma in situ, could be combined with photothermal destruction of targeted cancer cells using nanoparticle-based probes. This would provide a method for removing the cancer cells in the lymph nodes while preserving, largely intact, the lymphatic system of the cancer patient. As markers become available this general approach should be extendable to additional strategies for the treatment of metastatic disease.
The centers of solid tumors are frequently observed to be largely necrotic, resulting from prolonged hypoxia: insufficient availability of oxygen and glucose to meet the metabolic demands of the malignant cells. Because of the decreased blood flow in these tumor regions, they are inaccessible by, and therefore highly resistant to, conventional chemotherapies. One possible scenario for the progression of cancer to its latter, highly fatal stages is that cells surviving in these inaccessible hypoxic regions may themselves be the source of subsequent local recurrence and distant metastasis. One of the body’s responses to the presence of a malignant neoplasm is to recruit peripheral blood monocytes into the tumor, which then differentiate into macrophages. These cells have been shown to promote metastatic disease. One potentially promising scenario is to induce uptake of nanoshells into monocytes, which are then recruited into the hypoxic regions of tumors: the presence of the nanoshells would then permit photothermal destruction of the necrotic region. This type of approach may provide a critical new strategy for thwarting tumor metastasis.
An exciting new use of nanoparticle-assisted photothermal therapy is in delivery methods for gene therapy. It is widely recognized that gene-based therapies hold extraordinary therapeutic promise for cancer: many genetic markers have been discovered, and numerous DNA-based therapeutics have been proposed for the targeting of pathogenic genes for various cancers. Genetic vaccines have also been suggested for certain forms of cancer now believed to have a hereditary basis, such as the 42–57% of prostate cancer cases that correlate with inherited genetic factors. However, while the discovery of gene targets and the development of gene-based therapies at the molecular level has been pursued aggressively for more than 15 years, the transition of these therapies from the research laboratory to the clinic is at a virtual impasse and fraught with severe challenges. Unprotected gene therapy drugs (DNA- or RNA-based) introduced into the bloodstream are rapidly broken down, preventing their diffusion to the region of disease. Viruses, the initial carrier of choice in most gene therapy research, present a variety of potential problems to the patient – toxicity, immune and inflammatory responses, and gene control and targeting issues. The first clinical gene therapy studies utilizing a viral delivery vector resulted in patient death, and had to be terminated in their initial stage. There is a clear critical need for nonviral delivery vectors for gene therapy for this field to advance towards its many clinical applications. Nanoparticle–biomolecule light-actuated complexes are being developed and tested with clinically relevant genetic markers. For example, by combining gold nanoparticles with specific oligonucleotides, the nanoparticle complex can serve as a nonviral gene-delivery vector, where incident light can trigger the release of the nucleotide once the complex has been taken up by cells. Initial release data in cell culture studies show that this approach has outstanding promise for gene delivery. Light-triggered nucleotide release from these nanoparticle–molecule complexes makes them particularly well suited for the localized administration of gene therapy drugs into the tissue or organ of interest.
In conclusion, nanoparticle-assisted, photothermal therapeutic strategies have the capability of providing revolutionary tools in many battles against human disease, with the clear potential for highly effective therapy for cancer and other diseases. Moreover, this approach is unparalleled in its level of noninvasiveness and in its low, essentially nonexistent toxicity. The long-term impact of the development of these new treatment methods will be to change the way we treat cancer. This approach may also provide effective new strategies for treatments of other, lesser known and less-studied diseases such as autoimmune disorders, where few or no treatment options currently exist. In addition to increased efficacy, an extraordinary advantage of nanoparticle-assisted photothermal therapy is that essentially no, or minimal, side effects are expected. Replacing current chemotherapy treatments, with their high level of systemic toxicity and deleterious side effects, with this benign therapeutic approach will greatly increase the quality of life for cancer patients and their families.
Financial & competing interests disclosure The author is the inventor of nanoshells and pioneered nanoparticle-based photothermal therapies along with her collaborators at Rice University (TX, USA), J West and R Drezek. She is the co-founder of Nanospectra Biosciences, Inc. (http://www.nanospectra.com/), a Houston-based company dedicated to the translation of this therapeutic approach into clinical practice. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Source >http://www.futuremedicine.com/doi/full/10.2217/nnm.09.26
Wednesday, June 10, 2009
Biomedical devices
The devices considered in this section fall into the category of nanobiotechnology, also known as nanomedicine, defined as the application of nanotechnology to human health.One of the most attractive candidate tasks for a radically new approach is the sequencing ofthe human genome. The growing fund of medical experience concerning individual patients’responses to pharmaceutical drugs is revealing significant differences between individuals, whichin many cases might be due to differences in DNA sequence. Despite the tremendousboost to the technology of DNA sequencing that came from the international project to sequencethe (putatively prototypical) human genome, the basic methods applied were the conventionalbiochemical ones; the vast increase in throughput was achieved through massive parallelizationand automation.
The four different DNA “bases” (or nucleotides, symbolized as A,C,G,T) differ not only in the chemical nature, but also in their physical nature, most significantly as regards size and shape.One of the early motivations for developing the atomic force microscope was the hope that thesephysical differences could be revealed by rapidly scanning a single strand of DNA. Although theresolution, at least in the presence of liquid water, has so far proved to be inadequate, alternativeapproaches with the same end in view are being intensively investigated. The favoured schemeis to pass the DNA strand through a nanopore while measuring ionic conductance (of theelectrolyte solution in which the DNA is dissolved), either along or across the pore, with theresolution of a single base. The different nucleotides can be thus distinguished, but it is difficultto capture the DNA and drive it through the pore.
The flagship nanomedical system (rather than device) is the “nanobot”, an autonomous robotenvisaged to be about the size of a bacterium (i.e., about one micrometre in diameter), andcontaining many nanodevices (an energy source, a means of propulsion, an information pro-cessor, environmental sensors, and so forth). When engineering such devices it is importantto note the environment in which they must operate: viscous (highly dissipative), dominatedby friction and fluctuations (Brownian motion), and in which inertia plays a negligible role.This is in contrast to the familiar macroscopic mechanisms that follow Newton’s laws: for thenanobot, force is not given by the product of mass and acceleration, but by the product of thecoefficient of friction and its velocity, together with superimposed random fluctuations. Anyself-propelling nanobot is therefore likely to resemble a motile bacterium rather than a deviceequipped with nanoscale oars or paddles.
Source: Jeremy Rameden," Nanotechnology " 2009
The four different DNA “bases” (or nucleotides, symbolized as A,C,G,T) differ not only in the chemical nature, but also in their physical nature, most significantly as regards size and shape.One of the early motivations for developing the atomic force microscope was the hope that thesephysical differences could be revealed by rapidly scanning a single strand of DNA. Although theresolution, at least in the presence of liquid water, has so far proved to be inadequate, alternativeapproaches with the same end in view are being intensively investigated. The favoured schemeis to pass the DNA strand through a nanopore while measuring ionic conductance (of theelectrolyte solution in which the DNA is dissolved), either along or across the pore, with theresolution of a single base. The different nucleotides can be thus distinguished, but it is difficultto capture the DNA and drive it through the pore.
The flagship nanomedical system (rather than device) is the “nanobot”, an autonomous robotenvisaged to be about the size of a bacterium (i.e., about one micrometre in diameter), andcontaining many nanodevices (an energy source, a means of propulsion, an information pro-cessor, environmental sensors, and so forth). When engineering such devices it is importantto note the environment in which they must operate: viscous (highly dissipative), dominatedby friction and fluctuations (Brownian motion), and in which inertia plays a negligible role.This is in contrast to the familiar macroscopic mechanisms that follow Newton’s laws: for thenanobot, force is not given by the product of mass and acceleration, but by the product of thecoefficient of friction and its velocity, together with superimposed random fluctuations. Anyself-propelling nanobot is therefore likely to resemble a motile bacterium rather than a deviceequipped with nanoscale oars or paddles.
Source: Jeremy Rameden," Nanotechnology " 2009
Trends in Biomedical Nanotechnology(1)
Trends in Biomedical Nanotechnology Programs Worldwide
By Mark Morrison and Ineke Malsch
An overview of trends in nanotechnology research programs for biomedical applications in the United States, leading European countries, and Japan. We focus on technologies for applications inside the body, including drug delivery technologies for pharmaceuticals, and new materials and technologies for prostheses and implants. We also include technologies for applications outside the body including diagnostics and high throughput screening of drug compounds. We cover the main application areas in pharmaceuticals and medical devices — areas where governments expect nanotechnology to make important contributions. We also outline the currently operational national and European Union (EU) policies and programs intended to stimulate the development of biomedical nanotechnology in the U.S., Europe, and Japan.
Several applications of nanotechnology are already available in the market. Lipid spheres (liposomes) with diameters of 100 nm are available for carrying anticancer drugs inside the body. Some anti-fungal foot sprays contain nanoscale zinc oxide particles to reduce clogging.
Nanotechnology is producing short-term impacts in the areas of:
Medical diagnostic tools and sensors
Drug delivery
Catalysts (many applications in chemistry and pharmaceuticals)
Alloys (e.g., steel and materials used in prosthetics) Improved and body-friendly implants
Biosensors and chemical sensors
Bioanalysis tools Bioseparation technologies Medical imaging
Filters
Most current applications utilize nanopowder qualities instead of other properties present at the nanoscale. The next stage of applications of nanotechnology will allow products to exhibit more unusual properties as product creation is approached from the bottom up. This is considered a measure of the development of nanotechnology. Long-term product and application perspectives of nanotechnology with high future market potentials include:
Perfect selective sensors for the control of environment, food, and body functions Pharmaceuticals that have long-term dosable capabilities and can be taken orally Replacements for human tissues and organs
Economical or reusable diagnostic chips for preventive medical surveys
It is estimated that more than 300 companies in Europe are involved in nano- technology as their primary areas of business, and many more companies, particu- larly larger organizations, are pursuing some activities in the field. Large organiza- tions currently exploring the possibilities of nanotechnology with near-term applications in drug delivery are Biosante, Akzo Nobel, Ciba, Eli Lilly, and Merck.
Source:Biomedical nanotechnology / edited by Neelina H. Malsch
Tuesday, June 9, 2009
Lab on a chip
Lab on a chip mimics brain chemistry
February 12th, 2008 Johns Hopkins researchers from the Whiting School of Engineering and the School of Medicine have devised a micro-scale tool – a lab on achip – designed to mimic the chemical complexities of the brain. The system should help scientists better understand how nerve cells in the brain work together to form the nervous system.
AmpliChip CYP450 Test – www.AmpliChip.us
Roche Diagnostics US Official Site FDA cleared CYP450 Test
A report on the work appears as the cover story in the February 2008 issue of the British journal Lab on a Chip. ”The chip we’ve developed will make xperiments on nerve cells more simple to conduct and to control,” says Andre Levchenko, Ph.D., associate professor of biomedical engineering at the Johns Hopkins Whiting School of Engineering and faculty affiliate of the Institute for NanoBioTechnology. Nerve cells decide which direction to grow by sensing both the chemical cues flowing through their environment as well as those attached to the surfaces that surround them. The chip, which is made of a plastic-like substance and covered with a glass lid, features a system of channels and wells that allow researchers to control the flow of specific chemical cocktails around single nerve cells.
“It is difficult to establish ideal experimental conditions to study how neurons react to growth signals because so much is happening at once that sorting out nerve cell connections is hard, but the chip, designed by experts in both brain chemistry and engineering, offers a sophisticated way to sort things out,” says Guo-li Ming,
M.D.,Ph.D., associate professor of neurology at the Johns Hopkins School of Medicine and Institute for Cell Engineering.
In experiments with their chip, the researchers put single nerve cells, or rons,onto the chip then introduced specific growth signals (in the form of hemicals).They found that the growing neurons turned and grew toward higher concentrations of certain chemical cues attached to the chip’s surfaces, as well as to signaling molecules free-flowing in solution.
When researchers subjected the neurons to conflicting signals (both surface bound and cues in solution), they found that the cells turned randomly, suggesting that cells do not choose one signal over the other. This,according to Levchenko,supports the prevailing theory that one cue can elicit different responses depending on
a cell’s surroundings. “The ability to combine several different stimuli in the chip resembles a more realistic environment that nerve cells will encounter in the living animal,” Ming says.This in turn will make future studies on the role of neuronal cells in development and regeneration more accurate and complete.
Source: Johns Hopkins Medical Institutions
Nanoparticles Home in on Brain Cancer
Nanoparticles Home in on Brain Cancer
By Nikhil Swaminathan
November 17, 2006
Call them laser-guided smart bombs for brain tumors. Researchers at the University of Michigan announced the testing of a drug delivery system that involves drug-toting nanoparticles and a guiding peptide to target cancerous cells in the brain. Their study finds that via this method more of the drug can be delivered to a tumor's general vicinity. They report their findings in the November 15 issue of Clinical Cancer Research.
The researchers used a pharmaceutical called Photofrin, which is photodynamic, meaning it is activated by a laser after it has entered the bloodstream. As its primary side effect, the drug renders patients photosensitive, and they must remain out of bright sunlight and even unshaded lamps for up to 30 days after receiving treatment. Despite this major drawback, Photofrin is used in the treatment of esophageal, bladder and skin cancers. But their novel delivery system, which relies on the intravenous delivery of 40-nanometer-wide particles to carry the drug, may actually avoid much of the photosensitivity, because less Photofrin circulates in the bloodstream thanks to a peptide called F3. A sequence of 31 amino acids broken off of the protein HMGN2 (high mobility group protein 2), F3 has the ability to penetrate cell membranes. "This peptide acts as a "zip code" in that it enables the binding of the nanoparticles only to blood vessels within the tumor and not normal blood vessels," says Alnawaz Rehemtulla, a radiologist and environmental health scientist who co-authored the study. F3 can detect the expression of a protein called nucleolin, which is a marker on the surface of tumor cells.
Another problem the researchers avoided was having to deliver their medicine in such a way that it could cross the blood-brain barrier, which keeps many substances from entering the brain from the bloodstream. Typical chemotherapies must penetrate this shield to treat tumors. In this case, however, the nontoxic polyacrylamide particles didn't have to cross over via the bloodstream. "The nanoparticles do not need to cross the blood-brain barrier as they were specifically designed to target the blood vessel cells within the tumor," explains radiologist Brian Ross, one of the study's authors. "The treatment should be thought of as an antivascular treatment thereby shutting off the tumor blood flow resulting in the death of the tumor cells through starvation of oxygen and energy sources."
To test the delivery method, researchers divided 34 rats--all who received injections of cancerous cells into their brains--into different groups. Those that received no treatment or got only the laser fared poorly, dying on average within 8.5 days. Those that got Photofrin either intravenously or encapsulated in nanoparticles had a median survival time of 13 days. The group that got F3 with the Photofrin-carrying nanoparticles came through the best: they lived for, on average, 33 days; three of the five in this grouping lived for 60 days, and two of those three appeared tumor-free after six months. By using iron oxide as a contrast agent--to more easily detect where the nanoparticles ended up via MRI--the group determined that twice as much drug with the F3 peptide attached reached the tumor site--10 percent of the total amount administered--compared with when nontargeted nanoparticles were injected.
Ross says that based on the success of the study, the team is investigating if this delivery technology will work for nonphotodynamic therapies. Rehemtulla adds that if other FDA-approved chemotherapeutic agents reach their targets as successfully as Photofrin did, "then we will have developed a way to make cancer drugs more 'tumor-specific,' because they will only get into tumor vasculature and not normal vasculature. This will spare patients from normal tissue toxicity that is commonly associated with almost all chemotherapy."
Source>http://www.scientificamerican.com/article.cfm?id=nanoparticles-home-in-on
By Nikhil Swaminathan
November 17, 2006
Call them laser-guided smart bombs for brain tumors. Researchers at the University of Michigan announced the testing of a drug delivery system that involves drug-toting nanoparticles and a guiding peptide to target cancerous cells in the brain. Their study finds that via this method more of the drug can be delivered to a tumor's general vicinity. They report their findings in the November 15 issue of Clinical Cancer Research.
The researchers used a pharmaceutical called Photofrin, which is photodynamic, meaning it is activated by a laser after it has entered the bloodstream. As its primary side effect, the drug renders patients photosensitive, and they must remain out of bright sunlight and even unshaded lamps for up to 30 days after receiving treatment. Despite this major drawback, Photofrin is used in the treatment of esophageal, bladder and skin cancers. But their novel delivery system, which relies on the intravenous delivery of 40-nanometer-wide particles to carry the drug, may actually avoid much of the photosensitivity, because less Photofrin circulates in the bloodstream thanks to a peptide called F3. A sequence of 31 amino acids broken off of the protein HMGN2 (high mobility group protein 2), F3 has the ability to penetrate cell membranes. "This peptide acts as a "zip code" in that it enables the binding of the nanoparticles only to blood vessels within the tumor and not normal blood vessels," says Alnawaz Rehemtulla, a radiologist and environmental health scientist who co-authored the study. F3 can detect the expression of a protein called nucleolin, which is a marker on the surface of tumor cells.
Another problem the researchers avoided was having to deliver their medicine in such a way that it could cross the blood-brain barrier, which keeps many substances from entering the brain from the bloodstream. Typical chemotherapies must penetrate this shield to treat tumors. In this case, however, the nontoxic polyacrylamide particles didn't have to cross over via the bloodstream. "The nanoparticles do not need to cross the blood-brain barrier as they were specifically designed to target the blood vessel cells within the tumor," explains radiologist Brian Ross, one of the study's authors. "The treatment should be thought of as an antivascular treatment thereby shutting off the tumor blood flow resulting in the death of the tumor cells through starvation of oxygen and energy sources."
To test the delivery method, researchers divided 34 rats--all who received injections of cancerous cells into their brains--into different groups. Those that received no treatment or got only the laser fared poorly, dying on average within 8.5 days. Those that got Photofrin either intravenously or encapsulated in nanoparticles had a median survival time of 13 days. The group that got F3 with the Photofrin-carrying nanoparticles came through the best: they lived for, on average, 33 days; three of the five in this grouping lived for 60 days, and two of those three appeared tumor-free after six months. By using iron oxide as a contrast agent--to more easily detect where the nanoparticles ended up via MRI--the group determined that twice as much drug with the F3 peptide attached reached the tumor site--10 percent of the total amount administered--compared with when nontargeted nanoparticles were injected.
Ross says that based on the success of the study, the team is investigating if this delivery technology will work for nonphotodynamic therapies. Rehemtulla adds that if other FDA-approved chemotherapeutic agents reach their targets as successfully as Photofrin did, "then we will have developed a way to make cancer drugs more 'tumor-specific,' because they will only get into tumor vasculature and not normal vasculature. This will spare patients from normal tissue toxicity that is commonly associated with almost all chemotherapy."
Source>http://www.scientificamerican.com/article.cfm?id=nanoparticles-home-in-on
Monday, June 8, 2009
Age of Convergence
Nanomedicine is the medical application of nanotechnology. It covers areas such as nanoparticle drug delivery and possible future applications of molecular nanotechnology (MNT) and nanovaccinology. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials Nanomedicine research is directly funded, with the US National Institutes of Health in 2005 funding a five-year plan to set up four nanomedicine centers. In April 2006, the journal Nature Materials estimated that 130 nanotech-based drugs and delivery systems were being developed worldwide
In the near future, advancement in nanomedicine will deliver a valuable set of research tools and clinically helpful devices. The National Nanotechnology Initiative expects new commercial applications in the pharmaceutical industry that will include advanced drug delivery systems, new therapies, and in vivo imaging. The most important innovations are taking place in drug delivery which involves developing nanoscale particles or molecules to improve bioavailability. Bioavailability refers to the presence of drug molecules where they are needed in the body and where they will do the most good. Drug delivery focuses on maximizing bioavailability both at specific places in the body and over a period of time. Over 65 billion dollars is wasted every year because of poor bioavailability. In vivo imaging is another area where tools and devices are being developed. Using nanoparticle contrast agents, images such as ultrasound and MRI have a favorable distribution and improved contrast. The new therapies and surgeries that are being developed might be effective in treating illnesses and diseases such as cancer. Finally, a shift from the possible to the potential will be made when nanorobots such as neuro-electronic interfaces and cell repair machines are discussed. Drug delivery systems, lipid- or polymer-based nanoparticles, can be designed to improve the pharmacological and therapeutic properties of drugs. The strength of drug delivery systems is their ability to alter the pharmacokinetics and biodistribution of the drug. Nanoparticles have unusual properties that can be used to improve drug delivery. Where larger particles would have been cleared from the body, cells take up these nanoparticles because of their size. Complex drug delivery mechanisms are being developed, including the ability to get drugs through cell walls and into cells. Efficiency is important because many diseases depend upon processes within the cell and can only be impeded by drugs that make their way into the cell. Triggered response is one way for drug molecules to be used more efficiently. Drugs are placed in the body and only activate on encountering a particular signal. For example, a drug with poor solubility will be replaced by a drug delivery system where both hydrophilic and hydrophobic environments exist, improving the solubility. Also, a drug may cause tissue damage, but with drug delivery, regulated drug release can eliminate the problem. If a drug is cleared too quickly from the body, this could force a patient to use high doses, but with drug delivery systems clearance can be reduced by altering the pharmacokinetics of the drug. Poor biodistribution is a problem that can affect normal tissues through widespread distribution, but the particulates from drug delivery systems lower the volume of distribution and reduce the effect on non-target tissue. Potential nanodrugs will work by very specific and well-understood mechanisms, one of the major impacts of nanotechnology and nanoscience will be in leading development of completely new drugs with more useful behavior and less side effects.
In the near future, advancement in nanomedicine will deliver a valuable set of research tools and clinically helpful devices. The National Nanotechnology Initiative expects new commercial applications in the pharmaceutical industry that will include advanced drug delivery systems, new therapies, and in vivo imaging. The most important innovations are taking place in drug delivery which involves developing nanoscale particles or molecules to improve bioavailability. Bioavailability refers to the presence of drug molecules where they are needed in the body and where they will do the most good. Drug delivery focuses on maximizing bioavailability both at specific places in the body and over a period of time. Over 65 billion dollars is wasted every year because of poor bioavailability. In vivo imaging is another area where tools and devices are being developed. Using nanoparticle contrast agents, images such as ultrasound and MRI have a favorable distribution and improved contrast. The new therapies and surgeries that are being developed might be effective in treating illnesses and diseases such as cancer. Finally, a shift from the possible to the potential will be made when nanorobots such as neuro-electronic interfaces and cell repair machines are discussed. Drug delivery systems, lipid- or polymer-based nanoparticles, can be designed to improve the pharmacological and therapeutic properties of drugs. The strength of drug delivery systems is their ability to alter the pharmacokinetics and biodistribution of the drug. Nanoparticles have unusual properties that can be used to improve drug delivery. Where larger particles would have been cleared from the body, cells take up these nanoparticles because of their size. Complex drug delivery mechanisms are being developed, including the ability to get drugs through cell walls and into cells. Efficiency is important because many diseases depend upon processes within the cell and can only be impeded by drugs that make their way into the cell. Triggered response is one way for drug molecules to be used more efficiently. Drugs are placed in the body and only activate on encountering a particular signal. For example, a drug with poor solubility will be replaced by a drug delivery system where both hydrophilic and hydrophobic environments exist, improving the solubility. Also, a drug may cause tissue damage, but with drug delivery, regulated drug release can eliminate the problem. If a drug is cleared too quickly from the body, this could force a patient to use high doses, but with drug delivery systems clearance can be reduced by altering the pharmacokinetics of the drug. Poor biodistribution is a problem that can affect normal tissues through widespread distribution, but the particulates from drug delivery systems lower the volume of distribution and reduce the effect on non-target tissue. Potential nanodrugs will work by very specific and well-understood mechanisms, one of the major impacts of nanotechnology and nanoscience will be in leading development of completely new drugs with more useful behavior and less side effects.
Biomarker
Biomarker discovery is the process by which biomarkers are discovered. It is a medical term. Many commonly used blood tests in medicine are biomarkers. The way that these tests have been found can be seen as biomarker discovery. However, their identification has mostly been a one-at-a time approach. Many of these well-known tests have been identified based on clear biological insight, from physiology or biochemistry. This means that only a few markers at a time have been considered. One example of this way of biomarker discovery is the use of injections of inulin for measuring kidney function. From this, one discovered a naturally occurring molecule, creatinine, that enabled the same measurements to be made easily without injections. This can be seen as a serial process.
The recent interest in biomarker discovery is because new molecular biologic techniques promise to find relevant markers rapidly, without detailed insight into mechanisms of disease. By screening many possible biomolecules at a time, a parallel approach can be tried. Genomics and proteomics are some technologies that are used in this process. Significant technical difficulties remain. There is considerable interest in biomarker discovery from the pharmaceutical industry. Blood test or other biomarkers could serve as intermediate markers of disease in clinical trials, and also be possible drug targets.
Source:>http://bioinformations.info/nano-bioengineering.html
Friday, June 5, 2009
Nanoparticles Home in on Brain Cancer
Nanoparticles Home in on Brain Cancer
By Nikhil Swaminathan
November 17, 2006
Call them laser-guided smart bombs for brain tumors. Researchers at the University of Michigan announced the testing of a drug delivery system that involves drug-toting nanoparticles and a guiding peptide to target cancerous cells in the brain. Their study finds that via this method more of the drug can be delivered to a tumor's general vicinity. They report their findings in the November 15 issue of Clinical Cancer Research.
The researchers used a pharmaceutical called Photofrin, which is photodynamic, meaning it is activated by a laser after it has entered the bloodstream. As its primary side effect, the drug renders patients photosensitive, and they must remain out of bright sunlight and even unshaded lamps for up to 30 days after receiving treatment. Despite this major drawback, Photofrin is used in the treatment of esophageal, bladder and skin cancers. But their novel delivery system, which relies on the intravenous delivery of 40-nanometer-wide particles to carry the drug, may actually avoid much of the photosensitivity, because less Photofrin circulates in the bloodstream thanks to a peptide called F3. A sequence of 31 amino acids broken off of the protein HMGN2 (high mobility group protein 2), F3 has the ability to penetrate cell membranes. "This peptide acts as a "zip code" in that it enables the binding of the nanoparticles only to blood vessels within the tumor and not normal blood vessels," says Alnawaz Rehemtulla, a radiologist and environmental health scientist who co-authored the study. F3 can detect the expression of a protein called nucleolin, which is a marker on the surface of tumor cells.
Another problem the researchers avoided was having to deliver their medicine in such a way that it could cross the blood-brain barrier, which keeps many substances from entering the brain from the bloodstream. Typical chemotherapies must penetrate this shield to treat tumors. In this case, however, the nontoxic polyacrylamide particles didn't have to cross over via the bloodstream. "The nanoparticles do not need to cross the blood-brain barrier as they were specifically designed to target the blood vessel cells within the tumor," explains radiologist Brian Ross, one of the study's authors. "The treatment should be thought of as an antivascular treatment thereby shutting off the tumor blood flow resulting in the death of the tumor cells through starvation of oxygen and energy sources."
To test the delivery method, researchers divided 34 rats--all who received injections of cancerous cells into their brains--into different groups. Those that received no treatment or got only the laser fared poorly, dying on average within 8.5 days. Those that got Photofrin either intravenously or encapsulated in nanoparticles had a median survival time of 13 days. The group that got F3 with the Photofrin-carrying nanoparticles came through the best: they lived for, on average, 33 days; three of the five in this grouping lived for 60 days, and two of those three appeared tumor-free after six months. By using iron oxide as a contrast agent--to more easily detect where the nanoparticles ended up via MRI--the group determined that twice as much drug with the F3 peptide attached reached the tumor site--10 percent of the total amount administered--compared with when nontargeted nanoparticles were injected.
Ross says that based on the success of the study, the team is investigating if this delivery technology will work for nonphotodynamic therapies. Rehemtulla adds that if other FDA-approved chemotherapeutic agents reach their targets as successfully as Photofrin did, "then we will have developed a way to make cancer drugs more 'tumor-specific,' because they will only get into tumor vasculature and not normal vasculature. This will spare patients from normal tissue toxicity that is commonly associated with almost all chemotherapy."
Source>http://www.scientificamerican.com/article.cfm?id=nanoparticles-home-in-on
By Nikhil Swaminathan
November 17, 2006
Call them laser-guided smart bombs for brain tumors. Researchers at the University of Michigan announced the testing of a drug delivery system that involves drug-toting nanoparticles and a guiding peptide to target cancerous cells in the brain. Their study finds that via this method more of the drug can be delivered to a tumor's general vicinity. They report their findings in the November 15 issue of Clinical Cancer Research.
The researchers used a pharmaceutical called Photofrin, which is photodynamic, meaning it is activated by a laser after it has entered the bloodstream. As its primary side effect, the drug renders patients photosensitive, and they must remain out of bright sunlight and even unshaded lamps for up to 30 days after receiving treatment. Despite this major drawback, Photofrin is used in the treatment of esophageal, bladder and skin cancers. But their novel delivery system, which relies on the intravenous delivery of 40-nanometer-wide particles to carry the drug, may actually avoid much of the photosensitivity, because less Photofrin circulates in the bloodstream thanks to a peptide called F3. A sequence of 31 amino acids broken off of the protein HMGN2 (high mobility group protein 2), F3 has the ability to penetrate cell membranes. "This peptide acts as a "zip code" in that it enables the binding of the nanoparticles only to blood vessels within the tumor and not normal blood vessels," says Alnawaz Rehemtulla, a radiologist and environmental health scientist who co-authored the study. F3 can detect the expression of a protein called nucleolin, which is a marker on the surface of tumor cells.
Another problem the researchers avoided was having to deliver their medicine in such a way that it could cross the blood-brain barrier, which keeps many substances from entering the brain from the bloodstream. Typical chemotherapies must penetrate this shield to treat tumors. In this case, however, the nontoxic polyacrylamide particles didn't have to cross over via the bloodstream. "The nanoparticles do not need to cross the blood-brain barrier as they were specifically designed to target the blood vessel cells within the tumor," explains radiologist Brian Ross, one of the study's authors. "The treatment should be thought of as an antivascular treatment thereby shutting off the tumor blood flow resulting in the death of the tumor cells through starvation of oxygen and energy sources."
To test the delivery method, researchers divided 34 rats--all who received injections of cancerous cells into their brains--into different groups. Those that received no treatment or got only the laser fared poorly, dying on average within 8.5 days. Those that got Photofrin either intravenously or encapsulated in nanoparticles had a median survival time of 13 days. The group that got F3 with the Photofrin-carrying nanoparticles came through the best: they lived for, on average, 33 days; three of the five in this grouping lived for 60 days, and two of those three appeared tumor-free after six months. By using iron oxide as a contrast agent--to more easily detect where the nanoparticles ended up via MRI--the group determined that twice as much drug with the F3 peptide attached reached the tumor site--10 percent of the total amount administered--compared with when nontargeted nanoparticles were injected.
Ross says that based on the success of the study, the team is investigating if this delivery technology will work for nonphotodynamic therapies. Rehemtulla adds that if other FDA-approved chemotherapeutic agents reach their targets as successfully as Photofrin did, "then we will have developed a way to make cancer drugs more 'tumor-specific,' because they will only get into tumor vasculature and not normal vasculature. This will spare patients from normal tissue toxicity that is commonly associated with almost all chemotherapy."
Source>http://www.scientificamerican.com/article.cfm?id=nanoparticles-home-in-on
Nanocontainers Deliver Drugs
Nanocontainers Deliver Drugs Directly to Cells
By Sarah Graham
April 28, 2003
One challenge to effective drug treatment is getting the medication to exactly the right place. To that end, researchers have been investigating myriad new methods to deliver pharmaceuticals. Findings published in the current issue of the journal Science indicate that tiny nanocontainers composed of polymers may one day distribute drugs to specific spots within individual cells.
Radoslav Savic and his colleagues at McGill University tested the properties of tiny units built out of two types of polymers. The two compounds self-assemble into a spherical shape known as a micelle. One compound, which is hydrophobic (water fearing), aligns facing inwards and the other, which is hydrophilic (water loving), faces outwards. Drugs can then be loaded inside the tiny molecular globs, which measure 20 to 45 nanometers in diameter. The researchers used fluorescent labeling to track the micelles' journeys (see image). They found that the tiny containers could pass through the wall of a rat cell, but did not enter the cell's nucleus. The micelles did, however, penetrate some cell parts, such as mitochondria and the Golgi apparatus, which are important targets for drug delivery.
The scientists also determined that the micelles are very efficient at delivering their hydrophobic drug cargo once inside a cell. This property could mean that doctors may one day be able to administer smaller doses of toxic medications. "These micelles may thus be worth exploring for their potential to selectively deliver drugs to specified subcellular targets," the authors note. In an accompanying commentary, Jeffrey A. Hubbell of the University of Zurich cautions that much work remains to be done, "yet, multifunctional polymer micelles have already come a long way to reaching these ends."
Source >http://www.scientificamerican.com/article.cfm?id=nanocontainers-deliver-dr
By Sarah Graham
April 28, 2003
One challenge to effective drug treatment is getting the medication to exactly the right place. To that end, researchers have been investigating myriad new methods to deliver pharmaceuticals. Findings published in the current issue of the journal Science indicate that tiny nanocontainers composed of polymers may one day distribute drugs to specific spots within individual cells.
Radoslav Savic and his colleagues at McGill University tested the properties of tiny units built out of two types of polymers. The two compounds self-assemble into a spherical shape known as a micelle. One compound, which is hydrophobic (water fearing), aligns facing inwards and the other, which is hydrophilic (water loving), faces outwards. Drugs can then be loaded inside the tiny molecular globs, which measure 20 to 45 nanometers in diameter. The researchers used fluorescent labeling to track the micelles' journeys (see image). They found that the tiny containers could pass through the wall of a rat cell, but did not enter the cell's nucleus. The micelles did, however, penetrate some cell parts, such as mitochondria and the Golgi apparatus, which are important targets for drug delivery.
The scientists also determined that the micelles are very efficient at delivering their hydrophobic drug cargo once inside a cell. This property could mean that doctors may one day be able to administer smaller doses of toxic medications. "These micelles may thus be worth exploring for their potential to selectively deliver drugs to specified subcellular targets," the authors note. In an accompanying commentary, Jeffrey A. Hubbell of the University of Zurich cautions that much work remains to be done, "yet, multifunctional polymer micelles have already come a long way to reaching these ends."
Source >http://www.scientificamerican.com/article.cfm?id=nanocontainers-deliver-dr
Tuesday, May 12, 2009
Lab on a chip
Lab on a chip mimics brain chemistry
February 12th, 2008 Johns Hopkins researchers from the Whiting School of Engineering and the School of Medicine have devised a micro-scale tool – a lab on achip – designed to mimic the chemical complexities of the brain. The system should help scientists better understand how nerve cells in the brain work together to form the nervous system.
AmpliChip CYP450 Test – www.AmpliChip.us
Roche Diagnostics US Official Site FDA cleared CYP450 Test
A report on the work appears as the cover story in the February 2008 issue of the British journal Lab on a Chip. ”The chip we’ve developed will make xperiments on nerve cells more simple to conduct and to control,” says Andre Levchenko, Ph.D., associate professor of biomedical engineering at the Johns Hopkins Whiting School of Engineering and faculty affiliate of the Institute for NanoBioTechnology. Nerve cells decide which direction to grow by sensing both the chemical cues flowing through their environment as well as those attached to the surfaces that surround them. The chip, which is made of a plastic-like substance and covered with a glass lid, features a system of channels and wells that allow researchers to control the flow of specific chemical cocktails around single nerve cells.
“It is difficult to establish ideal experimental conditions to study how neurons react to growth signals because so much is happening at once that sorting out nerve cell connections is hard, but the chip, designed by experts in both brain chemistry and engineering, offers a sophisticated way to sort things out,” says Guo-li Ming,
M.D.,Ph.D., associate professor of neurology at the Johns Hopkins School of Medicine and Institute for Cell Engineering.
In experiments with their chip, the researchers put single nerve cells, or rons,onto the chip then introduced specific growth signals (in the form of hemicals).They found that the growing neurons turned and grew toward higher concentrations of certain chemical cues attached to the chip’s surfaces, as well as to signaling molecules free-flowing in solution.
When researchers subjected the neurons to conflicting signals (both surface bound and cues in solution), they found that the cells turned randomly, suggesting that cells do not choose one signal over the other. This,according to Levchenko,supports the prevailing theory that one cue can elicit different responses depending on
a cell’s surroundings. “The ability to combine several different stimuli in the chip resembles a more realistic environment that nerve cells will encounter in the living animal,” Ming says.This in turn will make future studies on the role of neuronal cells in development and regeneration more accurate and complete.
Source: Johns Hopkins Medical Institutions
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