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
แสดงบทความที่มีป้ายกำกับ NanoMedicine แสดงบทความทั้งหมด
แสดงบทความที่มีป้ายกำกับ NanoMedicine แสดงบทความทั้งหมด
วันจันทร์ที่ 15 มิถุนายน พ.ศ. 2552
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."
By Michael Berger. Copyright 2009 Nanowerk LLC >http://www.nanowerk.com/spotlight/spotid=10816.php
(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."
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
วันศุกร์ที่ 5 มิถุนายน พ.ศ. 2552
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
วันอังคารที่ 12 พฤษภาคม พ.ศ. 2552
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.
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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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