Nanomedicine Archive

Tuesday, March 16, 2010

Implanting Silicon Chips Into Cells May Soon Become a Possibility

Michael Berger at Nanowerk is reporting on recent research out of Spain to embed microelectronics within living cells, a feat that promises to provide intracellular sensing for research and medical monitoring applications. Turns out we're not very far away from this reality due to the nanoscale production of modern microprocessors.

A tidbit from Nanowerk:

In their experiments, the Spanish team fabricated different batches of polysilicon chips and then chose the most suitable device type with lateral dimensions of 1.5-3μm and with a thickness of 0.5 μm to be placed inside living cells. Cells were taken from Dictyostelium discoideum and human HeLa cells.
To further demonstrate the versatility of the technique, they studied the integration of different materials in a single chip and their 3D nanostructuring capability by using other common microelectronics techniques such as FIB milling.

After inserting the chips into the live cells, the researchers made sure that the cells remained alive and healthy. They found that over 90% of the chip-containing containing HeLa cell population remained viable 7 days after lipofection.

Read on at Nanowerk: Future bio-nanotechnology will use computer chips inside living cells...

Abstract in Small: Intracellular Silicon Chips in Living Cells

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Monday, March 15, 2010

Optically Driven Nanosensor May Become General Purpose Pathogen Detector

Scientists from Cornell and Tel Aviv universities have created a nanoelectromechanical system (NEMS) that can be used to sense the presence of very small concentrations of chemicals and microorganisms. Using an oscillating cantilever that wobbles at predictable frequencies depending on what is placed on it, the researchers are able to detect the nature of the object in the sensor. By generalizing the process and grouping large numbers of these cantilever systems together, they should be able to create a multipurpose sensor that can detect a wide range of pathogens and varying chemicals.

In past research, the team has demonstrated that by treating the cantilever with different substances, they can tell what other substances are present. For example, E. coli antibodies attached to the cantilever can detect the presence of E. coli in water.
The researchers have perfected the oscillators' design, Ilic [Rob Ilic, research associate at the Cornell NanoScale Science and Technology Facility] said, by laying their device on top of a layer of silicon dioxide, all of which rest on a silicon substrate. A pad with holes connects pegs of silicon dioxide, lined up like telephone poles, which eventually end at the cantilever.

A laser beam, switched on at the far end from the cantilever, travels down the device and causes the oscillator to wobble. The frequency is then measured by shining another laser on the oscillator and noting patterns in the reflected light.

The "telephone poles" allow the energy to move efficiently across the device by preventing it from buckling or sagging. The design makes it easy to read the resonant frequency of the cantilever.

In this process, the researchers discovered that over short distances, the energy from the laser came in the form of heat, which quickly dissipates. But when the laser was parked hundreds of microns away from the cantilever, the energy came in the form of acoustical waves that traveled through the device, dissipated more slowly, and allowed them to make their device longer.

Image: The nanoelectromechanical oscillator with the cantilever on the far right. The inset is a tilted 3-D profile of the structure, which shows the silicon dioxide posts.

Abstract in Journal of Applied Physics: Theoretical and experimental investigation of optically driven nanoelectromechanical oscillators

Press release: Nanoelectromechanical oscillators could lead to detection of harmful molecules, bacteria ...

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Tuesday, February 16, 2010

Nanoparticles are Proving Their Price in Gold in Fight on Cancer

In our previous coverage we've seen how researchers design gold nanoparticles for delivery into tumor cells, so these nanoagents can be energized by laser light to destroy their cellular hosts. The problem is that shining a laser is not practical for most cancers residing deep within the body. Researchers at Georgia Tech have now utilized gold nanoparticles as a tool to prevent cells from dividing and reproducing, potentially leading to an oncology tool that can put a full stop to the growth of a cancer.

From an abstract in Journal of The American Chemical Society:

By properly conjugating gold nanoparticles with specific peptides, we were successful in selectively transporting them to the nuclei of cancer cells. Confocal microscopy images of DNA double-strand breaks showed that localization of gold nanoparticles at the nucleus of a cancer cell damages the DNA. Gold nanoparticle dark-field imaging of live cells in real time revealed that the nuclear targeting of gold nanoparticles specifically induces cytokinesis arrest in cancer cells, where binucleate cell formation occurs after mitosis takes place. Flow cytometry results indicated that the failure to complete cell division led to programmed cell death (apoptosis) in cancer cells. These results show that gold nanoparticles localized at the nuclei of cancer cells have important implications in understanding the interaction between nanomaterials and living systems.

Press release with video of a cell unsuccessfully trying to divide: Using Gold Nanoparticles to Hit Cancer Where It Hurts ...

Abstract in Journal of The American Chemical Society: Nuclear Targeting of Gold Nanoparticles in Cancer Cells Induces DNA Damage, Causing Cytokinesis Arrest and Apoptosis

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Wednesday, February 10, 2010

Lasers Reveal Movement of Nanoparticles

Researchers have been looking for ways to track the movement of nanoparticles in biological tissue to study their in vivo interactions. Typically, attaching fluorophore molecules has been a common method to monitor nanoparticle movement, but these fluorophores have a limited lifetime and so are not practical for longer observations. Now scientists from Rice University are reporting in the Proceedings of the National Academy of Sciences the use of lasers to reveal the displacement and orientation of gold nanoparticles.

Gold nanorods can be "lit up" at will. Lasers at particular wavelengths excite surface plasmons that absorb the energy and emit a heat signature that can be detected by a probe laser. Because plasmons are highly polarized along a nanorod's length, reading the signal while turning the polarization of the laser tells researchers precisely how the rod is oriented.
An electron microscope photo from the new paper shows nanorods about 75 nanometers long and 25 nanometers wide on a glass slide at 90-degree angles to each other. An adjacent photothermal image shows them as pixilated smudges. The smudges are strongest when the laser polarization aligns lengthwise with the nanorods, but they disappear when the laser polarization and rods are 90 degrees out of phase.

"With plasmonics, you always have two properties: absorption and scattering," Link said. "Depending on the size, one or the other dominates. What's unique is that it's now possible to do both on the same structure or do it individually -- so we can only measure absorption or only measure scattering."

Nanorods much smaller than 50 nanometers are not detectable by some scattering methods, Link said, but photothermal detection should work with metallic particles as small as five nanometers; this makes them useful for biological applications.

Image: The graph at left shows how nanorods photographed in an electron microscope at right appear and disappear, based on their orientation, when their photothermal signatures are detected with polarized lasers.

Nano imaging takes turn for the better ...

Abstract in PNAS: Plasmonic nanorod absorbers as orientation sensors

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Friday, February 5, 2010

Nanoparticles Create Tiny Explosions to Destroy Cancer Cells

New cancer targeting nanoparticles seem like daily news here at Medgadget. Today we have gold nanoparticles developed jointly by researchers at Rice University and A.V. Lykov Heat and Mass Transfer Institute in Minsk, Belarus that create plasmonic nanobubbles when targeted with a laser. These particles can be guided to a tumor by antibodies and then activated to generate tiny explosions, so clinicians one day will be able to stay back and enjoy.

The short-lived bubbles are very bright and can be made smaller or larger by varying the power of the laser. Because they are visible under a microscope, nanobubbles can be used to either diagnose sick cells or to track the explosions that are destroying them.
In laboratory studies published last year, Dmitri Lapotko and colleagues at the Laboratory for Laser Cytotechnologies at the A.V. Lykov Heat and Mass Transfer Institute in Minsk, Belarus, applied nanobubbles to arterial plaque. They found that they could blast right through the deposits that block arteries.

In the current study, Lapotko and Rice colleague Jason Hafner, associate professor of physics and astronomy and of chemistry, tested the approach on leukemia cells and cells from head and neck cancers. They attached antibodies to the nanoparticles so they would target only the cancer cells, and they found the technique was effective at locating and killing the cancer cells.

Lapotko said the nanobubble technology could be used for "theranostics," a single process that combines diagnosis and therapy. In addition, because the cell-bursting nanobubbles also show up on microscopes in real time, Lapotko said the technique can be used for post-therapeutic assessment, or what physicians often refer to as "guidance."

Press release: Rice physicists kill cancer with 'nanobubbles'

More at Nanowerk: Plasmonic nanobubbles combine diagnosis and treatment in one theranostic method...

Abstract in Nanotechnology: Tunable plasmonic nanobubbles for cell theranostics

Image: Ajda Gregorcic

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Tuesday, February 2, 2010

Magnetic Nanoparticles Latch On, Ferry Cancer Cells Out of Body

A couple years ago researchers from Georgia Tech tested the ability of special magnetic nanoparticles to actually remove cancer cells out diseased tissue of lab mice. Following up on that work, the team recently submitted positive results of a similar experiment performed using human ovarian cancer cells. Although currently still in the laboratory stage of development, the technique may one day help prevent the spread of metastatic cancer cells to healthy and unaffected organs.

From the study abstract in Nanomedicine:

A majority of ovarian cancer metastases result from the shedding of malignant cells from the primary tumor into the abdominal cavity. Free-floating cancer cells in serous effusions of late-stage ovarian cancer patients may spread to internal organs making effective treatment extremely difficult. Selective removal of ovarian cancer cells from serous fluids may abate metastasis and improve long-term prognoses. We have previously shown that superparamagnetic nanoparticles conjugated to an ephrin-A1 mimetic peptide with a high affinity for the EphA2 receptor can be used to capture and remove cultured human ovarian cancer cells from the peritonea of experimental mice. Here we demonstrate the potential clinical utility of the methodology by in vitro capture and isolation of cancer cells from the ascites fluid of ovarian cancer patients.

Press release: Magnetic Nanoparticles Show Promise for Combating Human Cancer

Abstract in Nanomedicine: Selective removal of ovarian cancer cells from human ascites fluid using magnetic nanoparticles

Image: Nanoparticles, in brown, attach themselves to cancer cells, in violet, from the human abdominal cavity. Credit: Ken Scarberry/Georgia Tech

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Monday, February 1, 2010

Nanocorals Developed to Attack Tumor Cells

UC Berkeley researchers have developed a new type of nanoparticle that can selectively target tumor cells and report back the presence of certain molecular markers found in its environment. The dual sided nanoparticle uses a polystyrene region on one side for cell binding and a gold region on the other for label-free biomolecular sensing capabilities via strong surface-enhanced Raman spectroscopy (SERS) signal. The technology provides an opportunity to develop therapies that find and kill cancer cells and also verify the success of treatment.

The statement from UC Berkley explains:

The tiny probes measure a few hundred nanometers in diameter — one-thousandth the width of a human hair, and one-hundredth the size of most cancer cells. The team’s insight was to combine different materials — roughened gold on one side, and smooth polystyrene on the other — onto a single probe...
The sensing side of the nanocoral relies upon a technique called surface-enhanced Raman spectroscopy (SERS), which takes advantage of the electromagnetic excitations that occur as molecules make contact with the roughened surface of a metal, such as gold. Molecules produce oscillations that resonate at signature frequencies when exposed to laser light, revealing their presence to the scientists.

The researchers verified the sensitivity of the nanocoral by measuring its ability to detect a standard chemical compound for Raman spectroscopy.

To get the nanocoral to target specific cells, the researchers took advantage of the capability to attach antibodies to polymer surfaces.

"We can tailor the nanocoral to cancer cells of interest by attaching the appropriate antibodies," said the study's other co-lead author, Liz Wu, who conducted this research as a Ph.D. student in the Applied Science and Technology program.

The researchers demonstrated this concept by coating the polystyrene surface with antibodies that attack human epidermal growth factor receptor 2 (HER-2), a well-known target for cancer treatment since it is often over-expressed in aggressive forms of breast cancer. They confirmed with both bright field and fluorescent images that the nanocoral attached to breast cancer cells with HER-2 receptors, while control experiments showed that no binding occurred when different antibodies or when cells lacking HER-2 were used.

Full story: Engineers develop cancer-targeting nanoprobe sensors...

Abstract in Small: Bioinspired Nanocorals with Decoupled Cellular Targeting and Sensing Functionality

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Wednesday, January 20, 2010

Nanodiamonds Significantly Improve Performance of MRI Contrast Agent

Scientists at Northwestern University have been tinkering with nanodiamonds, tiny versions of the common variety that have a regular carbon structure, to discover interesting and practical properties of the material. (See Medgadget's flashbacks below.) After demonstrating the general biocompatibility of nanodiamonds, the researchers are now learning how to advance these particles into the clinical arena. A new finding, just published in Nano Letters, is paving way for an impressive increase in Gadolinium contrast imaging during MRI procedures. By attaching nanodiamonds to molecules containing Gd, the researchers noted a significantly improved contrast resolution in MRI images.

Ho [Dean Ho, assistant professor of biomedical engineering and mechanical engineering] and Meade [Thomas J. Meade, professor in cancer research] imaged a variety of nanodiamond samples, including nanodiamonds decorated with various concentrations of Gd(III), undecorated nanodiamonds and water. The intense signal of the Gd(III)-nanodiamond complex was brightest when the Gd(III) level was highest.
"Nanodiamonds have been shown to be effective in attracting water molecules to their surface, which can enhance the relaxivity properties of the Gd(III)-nanodiamond complex," said Ho. "This might explain why these complexes are so bright and such good contrast agents."

"The nanodiamonds are utterly unique among nanoparticles," Meade said. "A nanodiamond is like a cargo ship -- it gives us a nontoxic platform upon which to put different types of drugs and imaging agents."

The biocompatibility of the Gd(III)-nanodiamond complex underscores its clinical relevance. In addition to confirming the improved signal produced by the hybrid, the researchers conducted toxicity studies using fibroblasts and HeLa cells as biological testbeds.

They found little impact of the hybrid complex on cellular viability, affirming the complex's inherent safety and positioning it as a clinically significant nanomaterial. (Other nanodiamond imaging methods, such as fluorescent nanodiamond agents, have limited tissue penetration and are more appropriate for histological applications.)

Nanodiamonds are carbon-based materials approximately four to six nanometers in diameter. Each nanodiamond's surface possesses carboxyl groups that allow a wide spectrum of compounds to be attached to it, not just gadolinium(III).

The researchers are exploring the pre-clinical application of the MRI contrast agent-nanodiamond hybrid in various animal models. With an eye towards optimizing this novel hybrid material, they also are continuing studies of the structure of the Gd(III)-nanodiamond complex to learn how it governs increased relaxivity.

Northwestern press release: Game-changing Nanodiamond Discovery for MRI...

Abstract in Nano Letters: Gd(III)-Nanodiamond Conjugates for MRI Contrast Enhancement

Flashbacks: Nanodiamonds Serve as Transport Mechanism for Therapeutic Insulin; NanoDiamonds...Everyone's Friend?; Nanofountain Delivers Therapeutic Particles Into Cells

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Researchers Disrupt Oncogene Expression by Delivering siRNA Into Malignant Cells

Nanowerk is reporting on recent work by researchers at UCLA to use siRNA (small interfering RNA) laden quantum dots to knockdown cancer genes within neoplastic cells. Although various applications for siRNA have been developed, this new work is a major step in bringing the nanotechnology into practice for clinical research or even as a viable treatment option.

Michael Berger over at Nanowerk reports:

The researchers' goal was to use the RNAi-based approach to specifically inhibit the PI3K/Akt signaling pathway – a key signal cascade for cancer cell proliferation and apoptosis – in brain tumor cells, which were surrounded by non-malignant cells, thus demonstrating the target specificity of a class of siRNA quantum dots (siRNA-QDs) that they developed.
In new work published by Lee's team and collaborators at UCLA ("Selective Inhibition of Human Brain Tumor Cells through Multifunctional Quantum-Dot-Based siRNA Delivery"), the researchers first optimized their system by knocking down the expression of enhanced green fluorescent proteins (EGFP), and then using this optimized system they successfully suppressed the expression of EGFRvIII (epidermal growth factor receptor variant III) in the human GBM cell line, which subsequently led to cell apoptosis.

Read on at Nanowerk: Quantum dot based siRNA approach selectively inhibits brain cancer cells...

Abstract in Angewandte Chemie International Edition: Selective Inhibition of Human Brain Tumor Cells through Multifunctional Quantum-Dot-Based siRNA Delivery

Image: Multifunctional siRNAQDs (red), when incubated in a co-culture of malignant tumor cells (U87-EGFP) and less tumorigenic cells (SK-N-BE(2)C), selectively transfected the U87 cells. Very few siRNA-QDs internalized within the less tumorigenic cells. (Scale bar = 50 µm).

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Tuesday, January 19, 2010

'Nanoburrs' Stick to and Deliver Drugs to Damaged Arteries

Researchers at Harvard and MIT have designed new novel nanoparticles to treat atherosclerosis. The particles have a "sticky" outer coating which attaches to tissue basement membrane, something that is only exposed in damaged portions of the arterial wall. In this fashion, once injected into the bloodstream the particles will "seek out" arteries that need treatment. Once stuck, the particles slowly release a drug, paclitaxel, that slows and potentially reverses the closing off of that artery.

The new technology is designed to be used in conjunction with stents, and also to be used in areas where stent placement would not be feasible. In one experiment, the researchers injected the particles into a rat tail, where they subsequently traveled through the bloodstream and attached to the rats damaged left carotid artery. This exciting technology is currently undergoing further refinement and animal testing.

Tuesday, January 12, 2010

Nano Needlese Inject Molecules Into Cells

Researchers from Harvard University and Korea Institute of Science and Technology in Seoul are working on a method for introducing molecules into the insides of cells with the help of silicon nanowires. Current methods can be clunky and often require the use of viruses and proteins to ferry molecules, meaning that only certain methods work for a given type of cells. By growing cells on top of specially prepared nanowires, the research team believes that just about any molecule can be introduced into most any type of cell, which may lead to a standard new methodology in biochemistry labs.

Technology Review explains with more details:

To use the nanowires to deliver molecules, Park's team first treated them with a chemical that would allow molecules to bind relatively weakly to the surface of the nanowires, then coated the wires with a molecule or combination of molecules of interest. When cells are impaled on the nanowires, the molecules are released into the cells' interior. The chemical treatment of the wires could potentially be manipulated to control the binding and release of molecules--releasing them more slowly, for instance--and the wires can be constructed at different lengths to reach different parts of the cell. To demonstrate the method's flexibility, the team used the approach to deliver chemicals, small RNA molecules, DNA, and proteins into a range of cell types.
The beds of nanowires can be arranged on microarrays suitable for rapid experiments and imaging cells under a microscope. These microarrays can be "printed" with different patterns or combinations of molecules, making it possible to test many different molecules at once on an array of cells. The authors believe it could be possible to screen 20,000 different proteins or other chemicals on cells within a single microscopic slide.

More at Technology Review: Needling Molecules...

Abstract in PNAS: Vertical silicon nanowires as a universal platform for delivering biomolecules into living cells

Image: Rat neurons growing normally on a bed of nanowires. Credit: Hongkun Park

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Friday, January 8, 2010

Polymeric Protein Encapsulation May Bring Protein Therapy to Practical Reality

Protein therapy, or direct replacement of problematic proteins within cells, has been looked into as a possible alternative to gene therapy. Gene therapy is currently used in certain cases to fix the production of defective proteins, but there is a real potential for side effects when messing with one's DNA. The problem with delivering proteins is that they are often metabolized by the body and few actually get to where they're needed. Researchers at UCLA have now developed a method to encapsulate proteins within a polymer shell that can provide safe transport to the target therapy site.

The nanocapsules consist of a single-protein core and thin polymer shell anchored covalently to the protein core. Depending on whether degradable or non-degradable crosslinkers are used in synthesizing the nanocapsule, the skin of the capsule is either degradable or non-degradable. This is an important feature since for enzymes with large substrates, or other proteins that need to interact with other proteins inside the cell, a degradable capsule is essential.
Segura notes that the novel nanocapsules can improve current protein therapeutic delivery with regard to several aspects: increased stability of the protein against protease degradation; enhanced cellular internalization; endosomal escape; and the hydrogel capsule allows for the diffusion of small substrates inside the capsule, so if the protein at the core of the capsule is an enzyme the enzyme is able to catalyze a reaction without degrading the capsule.

"The protein cores can be chosen from a vast library of proteins, including enhanced green fluorescent protein, horseradish peroxidase, bovine serum albumin, superoxide dismutase and caspase-3, which makes this a very versatile delivery platform" says Segura. "This method can also be generalized to multiple protein delivery while maintaining low toxicity. Such a multiple protein delivery method has great potential for therapies in which proteins act synergistically or in tandem."

Image: (Left) Transmission electronic microscopic (TEM) image of single-protein nanocapsules with uniform size distribution (~30 nm in diameter) and (right) a schematic of the nanocapsule consisting of an encased protein and a skin layer of crosslinked polymer network. (Images: Professor Yunfeng Lu, UCLA)

Abstract in Nature Nanotechnology: A novel intracellular protein delivery platform based on single-protein nanocapsules

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Philips Developing New Bedside Biosensor for Rapid Disease Detection

Philips has been working on a disposable biosensor that is capable of detecting picomolar concentrations of proteins to be able to do molecular disease marker detection at the point of care. Currently clinicians send samples to the lab that practices traditional chemistry, often a laborious and time consuming process. The new system uses a cartridge that contains ligand molecules, attached to magnetic nanoparticles, that hone in on a protein in question. A magnetic field inside facilitates the sorting of nanoparticles carrying the target protein out of the rest of the liquid, and an optical unit to detect their concentration.

Philips explains:

The magnetic nanoparticles are preloaded into the cartridge during its manufacture and automatically disperse into the sample as the cartridge fills with blood. Coated with appropriate ligand molecules, they bind to target protein molecules in the sample blood. After a short time, typically around a minute, a large fraction of the target protein molecules end up being bound to the surface of the magnetic nanoparticles.

A small electromagnet situated beneath the cartridge then generates a magnetic field that attracts all the magnetic nanoparticles to the biosensor’s active surface, which is coated with ligand molecules that bind to a second binding site on the target protein. As a result of this magnetic attraction, the surface concentration of the target protein is significantly increased, which speeds up the binding process. The target protein molecules end up locked in a sandwich between the active surface on one side and attached nanoparticles on the other. This type of assay is therefore often referred to as a ‘sandwich assay’.

An electromagnet situated above the cartridge then generates a magnetic field that pulls unbound magnetic nanoparticles away from the active surface. In this way, a very fast and accurately controlled separation between bound and unbound magnetic nanoparticles is achieved, which replaces traditional washing steps. Because each magnetic nanoparticle that remains on the surface is bound there by a target protein molecule, the number of nanoparticles remaining at the surface is a measure of the target protein concentration in the blood sample.

In the final phase, the number of bound nanoparticles is measured using an optical technique based on frustrated total internal reflection. Illuminated at the correct angle, light hitting the underside of the sensor’s active surface is normally reflected without any loss in intensity (total internal reflection). However, when nanoparticles are bound to the opposite side of the surface they scatter and absorb the light, reducing the intensity of the reflected beam. These intensity variations in the reflected beam, which correspond to the number of bound nanoparticles, are detected by a CMOS image sensor similar to that used in a digital camera.

Images: Top: A) The magnetic nanoparticles are preloaded into the cartridge during its manufacture and automatically disperse into the sample as the cartridge fills with blood. Coated with appropriate ligand molecules, they bind to target protein molecules in the sample. B) A small electromagnet situated beneath the cartridge generates a magnetic field that attracts all the magnetic nanoparticles to the biosensor's active surface, which is coated with ligand molecules that bind to a second binding site on the target protein. C) An electromagnet situated above the cartridge generates a magnetic field that pulls unbound magnetic nanoparticles away from the active surface. Bottom: The target protein molecules end up locked in a sandwich between the active surface on one side and attached nanoparticles on the other. The number of attached nanoparticles is measured using an optical technique based on frustrated total internal reflection.

Press release: Magnotech: Philips' magnetic biosensor platform designed for point-of-care testing...

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Wednesday, January 6, 2010

Drug Ferrying Nanoparticles Pass Through Mucus Layer, Then Do Some Work

Getting drugs to pass through the mucus barrier is a major pharmacokinetic challenge as is, and it is an especially daunting task for the development of nano-based therapeutic agents. Ever since nanoparticles have been looked into as possible ferrying vehicles to overcome the mucus barrier problem, each either had trouble moving through the mucus or was not degradable so as to release their pharmacological cargo at the therapeutic site. Now Johns Hopkins University researchers created a biodegradable particle that can move through mucus and be preprogrammed to open in a time frame lasting from days to weeks.

The new biodegradable particles comprise two parts made of molecules routinely used in existing medications. An inner core, composed largely of polysebacic acid (PSA), traps therapeutic agents inside. A particularly dense outer coating of polyethylene glycol (PEG) molecules, which are linked to PSA, allows a particle to move through mucus nearly as easily as if it were moving through water and also permits the drug to remain in contact with affected tissues for an extended period of time.
In Hanes’ previous studies with mucus-penetrating particles, latex particles could be effectively coated with PEG but could not release drugs or biodegrade. Unlike latex, however, PSA can degrade into naturally-occurring molecules that are broken down and flushed away by the body through the kidney, for example. As the particles break down, the drugs loaded inside are released.

This property of PSA enables the sustained release of drugs, said Samuel Lai, assistant research professor in the Department of Chemical and Biomolecular Engineering, while designing them for mucus penetration allows them to more readily reach inaccessible tissues.

Jie Fu, an assistant research professor, also from the Department of Chemical and Biomolecular Engineering, said, “As it degrades, the PSA comes off along with the drug over a controlled amount of time that can reach days to weeks.”

Polyethylene glycol acts as a shield to protect the particles from interacting with proteins in mucus that would cause them to be cleared before releasing their contents. In a related research report, the group showed that the particles can efficiently encapsulate several chemotherapeutics, and that a single dose of drug-loaded particles was able to limit tumor growth in a mouse model of lung cancer for up to 20 days.

Images:This image shows the biodegradable nanoparticles produced by the Justin Hanes Lab at Johns Hopkins University as seen under a scanning electron microscope. Top: This biodegradable nanoparticle developed by the Justin Hanes Lab at Johns Hopkins University is shown here at microscale for easier viewing. The particle displays its polymer coating as a red fluorescent glow. Hanes' biodegradable nanoparticles have the ability to penetrate mucus barriers in the body to deliver drugs. Bottom:

Press release: Biodegradable Nanoparticles Can Bypass Mucus Barrier and Release Drugs Over Time...

Abstract in PNAS: Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier

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Tuesday, January 5, 2010

Combination of Nanoparticles Creates a More Powerful Cancer Targeting Tool

A collaborative effort of scientific institutions in California and Massachusetts has created a multi-prong tumor killing technology that uses two types of nanoparticles injected into the blood stream that cooperate to target and destroy tumors. The study, just published in the Proceedings of the National Academy of Sciences, describes how the nano brew was successfully applied to mice with epithelial tumors.

The first particle is a gold nanorod “activator’ that accumulates in tumors by seeping through its leaky blood vessels. The gold particles cover the whole tumor and behave like an antenna by absorbing otherwise benign infrared laser irradiation, which then heats up the tumor.
After the nanorods had circulated in the bloodstream of mice that had epithelial tumors for three days, the researchers used a weak laser beam to heat the rods that attached to the tumors. This sensitized the tumors, and the researchers then sent in a second nanoparticle type, composed of either iron oxide nanoworms or doxorubicin-loaded liposomes. This “responder” nanoparticle was coated with a special targeting molecule specific for the heat-treated tumor.

The researchers designed one type of responder particle with strings of iron oxide, which they called “nanoworms,” that show up brightly in a medical magnetic resonance imaging, or MRI, system. The second type is a hollow nanoparticle loaded with the anti-cancer drug doxorubicin. With the drug-loaded responder, the scientists demonstrated in their experiments that a tumor growing in a mouse can be arrested and then shrunk.

Images: Top: Gold nanorods accumulate in tumors. Bottom: Doxorubicin-loaded liposomes are designed to kill tumors.

UCSD press statement: Researchers Develop "Nano Cocktail" to Target and Kill Tumors...

Abstract in PNAS: Cooperative nanomaterial system to sensitize, target, and treat tumors

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Monday, December 28, 2009

Nano Level Magnetic Resonance Imaging May Reveal Smallest Life Processes

Researchers at Cornell University and U.S. Military Academy are working hard on development of a method to detect the magnetic imbalance of nitroxides, stable organic compounds that have an unpaired electron. Nitroxides can be attached to other molecules, and so there's a possibility to track just about anything at the nano level.

By creating a sample of nitroxide molecules dissolved in a thin-film polymer and bringing the sample close to a 4-micron nickel magnet attached to a 350-nanometer silicon cantilever, they can detect the electron spin by measuring the frequency of the cantilever as it wobbles, like a diving board. The cantilever is similar to those used in scanning probe microscopy, a type of imaging that involves a cantilever scanning a surface and recording the probe-surface interactions.

To improve their frequency readouts and get more accurate measurements, the group must learn, among others things, how to make their magnets smaller, Marohn said [John Marohn, associate professor of chemistry].

Full story at Cornell Chronicle: Researchers are on the path to creating nano-MRI images...

Abstract in PNAS: Scanned-probe detection of electron spin resonance from a nitroxide spin probe

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Tuesday, December 22, 2009

DNA Used to Control Nanostructure Configurations

Researchers at Brookhaven National Laboratory have adapted DNA strands as switching mechanisms for organizing nanoparticles into specific structures. This ability to switch between different nanostructure configurations may allow for the creation of biosensors and nanodevices that can perform specific tasks within the body.

The scientists achieved the goal of responsiveness by creating structures where the distance between nanoparticles could be carefully controlled with nanometer accuracy.
In their previous studies, the scientists used single strands of DNA attached to individual nanoparticles as linker molecules. When the free ends of these DNA strands had complementary genetic code, they would bind to attach the particles. Constraining the interactions by anchoring some of the particles on a surface allowed the scientists to reliably form a variety of structures from two-particle clusters (called dimers) to more complex 3-D nanoparticle crystals.

In the new work, the scientists have added more complicated double-stranded DNA structures. Unlike the single strands, which coil in uncontrollable ways, these double-stranded structures are more rigid and therefore constrain the interparticle distances.

Additionally, some of the strands making up the double-stranded DNA molecules have complicated structures such as loops, which pull the bound particles closer together than when both strands are exactly parallel. By varying the type of DNA device, between looped and unlooped strands, and measuring the interparticle distances using precision techniques at Brookhaven’s National Synchrotron Light Source (NSLS) and at the Center for Functional Nanomaterials (CFN), the scientists demonstrated that they could effectively control the distance between the particles and switch the system from one state to another at will.

The approach resulted in two-configuration, switchable systems both in dimers and nanocrystals, with a distance change of about 6 nanometers — about 25 percent of the interparticle distance. By comparing kinetics in the two systems, they found that the switching between states is faster in the simpler, two-particle system. The dimers also retain their ability to return to their initial state more precisely than the 3-D crystals, suggesting that molecular crowding may be an issue to further investigate in the 3-D materials.

Press release: Switchable Nanostructures Made with DNA...

Abstract in Nature Nanotechnology: Switching binary states of nanoparticle superlattices and dimer clusters by DNA strands

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Monday, December 21, 2009

Implantable Solar Cells Might Power Next Generation of In Vivo Devices

A collaboration between researchers from Donghua University in Shanghai, China and Max Planck Institute for Colloids and Interfaces in Potsdam, Germany has developed photovoltaic cells that can be used to recharge batteries in implanted devices by shining a near infrared laser beam through the skin.

Nanowerk reports:

They use rare earth upconverting nanophosphors to absorb 980 nm laser light and then emit visible luminescence which can subsequently excite traditional solar cells to produce electricity.
In their work, the research team determined that, under the irradiation of a 980-nm laser with a power of 1W, the visible up-converting luminescence of rare-earth nanophosphors can be efficiently absorbed by the dyes in 980LD-PVCs so that they exhibit a maximal output power of 0.47 mW.

In particular, after being covered with 1 to 6 layers of pig intestines (thickness: ca. 1mm per layer) as a model of biological tissues, 980LD-PVCs still possess a maximal output power of between 0.28 and 0.02 mW, which is efficient enough to drive many kinds of biodevices.

Abstract in Advanced Functional Materials: 980-nm Laser-Driven Photovoltaic Cells Based on Rare-Earth Up-Converting Phosphors for Biomedical Applications

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Friday, December 18, 2009

Live Tracking of Therapeutic Nanoparticles via MRI

Dozens, if not hundreds, of research teams around the world are developing nanoparticles that can deliver targeted forms of therapy directly to the cancer. One issue with bringing this technology to the clinic involves identifying when the particles have arrived at their target so that therapy can begin. Researchers from Rice University and Baylor College of Medicine (BCM) have now created nanoparticles that can be monitored as they move through the body in real-time on MRI.

The all-in-one particles are based on nanoshells -- particles [Naomi Halas, Rice Professor in Electrical and Computer Engineering] invented in the 1990s that are currently in human clinical trials for cancer treatment. Nanoshells harvest laser light that would normally pass harmlessly through the body and convert it into tumor-killing heat.
In designing the new particle, Halas partnered with Amit Joshi, assistant professor in BCM's Division of Molecular Imaging, to modify nanoshells by adding a fluorescent dye that glows when struck by near-infrared (NIR) light. NIR light is invisible and harmless, so NIR imaging could provide doctors with a means of diagnosing diseases without surgery.

In studying ways to attach the dye, Halas' graduate student, Rizia Bardhan, found that dye molecules emitted 40-50 times more light if a tiny gap was left between them and the surface of the nanoshell. The gap was just a few nanometers wide, but rather than waste the space, Bardhan inserted a layer of iron oxide that would be detectable with MRI. The researchers also attached an antibody that lets the particles bind to the surface of breast and ovarian cancer cells.

In the lab, the team tracked the fluorescent particles and confirmed that they targeted cancer cells and destroyed them with heat. Joshi said the next step will be to destroy whole tumors in live animals. He estimates that testing in humans is at least two years away, but the ultimate goal is a system where a patient gets a shot containing nanoparticles with antibodies that are tailored for the patient's cancer. Using NIR imaging, MRI or a combination of the two, doctors would observe the particles' progress through the body, identify areas where tumors exist and then kill them with heat.

Press release: Tracking new cancer-killing particles with MRI...

Abstract in Advanced Functional Materials: Nanoshells with Targeted Simultaneous Enhancement of Magnetic and Optical Imaging and Photothermal Therapeutic Response

Image credit: Wellcome Library

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