A New Drug Delivery Technique! "Nanoblasts" from laser-activated nanoparticles move molecules, proteins and DNA into cells!

Innovations in nanotechnology in medicine continue to happen rapidly! One of the most recent innovations has been  a new drug delivery technique. In this technique, "nanoblasts" or bursts of laser light are used to punch holes through cell membranes and deliver molecules, proteins and DNA into cells directly! This new method is revolutionary in the fact that in the future, nanomedicine could be delivered through rhis technology. Here is the full article:

"ScienceDaily (July 28, 2010) — Using chemical "nanoblasts" that punch tiny holes in the protective membranes of cells, researchers have demonstrated a new technique for getting therapeutic small molecules, proteins and DNA directly into living cells.

Carbon nanoparticles activated by bursts of laser light trigger the tiny blasts, which open holes in cell membranes just long enough to admit therapeutic agents contained in the surrounding fluid. By adjusting laser exposure, the researchers administered a small-molecule marker compound to 90 percent of targeted cells -- while keeping more than 90 percent of the cells alive.

The research was sponsored by the National Institutes of Health and the Institute of Paper Science and Technology at Georgia Tech. It will be reported in the August issue of the journal Nature Nanotechnology.





(Image above: A field of human prostate cancer cells is shown after exposure to laser-activated carbon nanoparticles. The cell membranes have been stained red to assist in visualization. Each of the red circles is a single cell. (Credit: Credit: Prerona Chakravarty)

"This technique could allow us to deliver a wide variety of therapeutics that now cannot easily get into cells," said Mark Prausnitz, a professor in the School of Chemical and Biomolecular Engineering at the Georgia Institute of Technology. "One of the most significant uses for this technology could be for gene-based therapies, which offer great promise in medicine, but whose progress has been limited by the difficulty of getting DNA and RNA into cells."

The work is believed to be the first to use activation of reactive carbon nanoparticles by lasers for medical applications. Additional research and clinical trials will be needed before the technique could be used in humans.

Researchers have been trying for decades to drive DNA and RNA more efficiently into cells with a variety of methods, including using viruses to ferry genetic materials into cells, coating DNA and RNA with chemical agents or employing electric fields and ultrasound to open cell membranes. However, these previous methods have generally suffered from low efficiency or safety concerns.
With their new technique, which was inspired by earlier work on the so-called "photoacoustic effect," Prausnitz and collaborators Prerona Chakravarty, Wei Qian and Mostafa El-Sayed hope to better localize the application of energy to cell membranes, creating a safer and more efficient approach for intracellular drug delivery.

Their technique begins with introducing particles of carbon black measuring 25 nanometers -- one millionth of an inch -- in diameter into the fluid surrounding the cells into which the therapeutic agents are to be introduced. Bursts of near-infrared light from a femotosecond laser are then applied to the fluid at a rate of 90 million pulses per second. The carbon nanoparticles absorb the light, which makes them hot. The hot particles then heat the surrounding fluid to make steam. The steam reacts with the carbon nanoparticles to form hydrogen and carbon monoxide.

The two gases form a bubble which grows as the laser provides energy. The bubble collapses suddenly when the laser is turned off, creating a shock wave that punches holes in the membranes of nearby cells. The openings allow therapeutic agents from the surrounding fluid to enter the cells. The holes quickly close so the cell can survive.

The researchers have demonstrated that they could get the small molecule calcein, the bovine serum albumin protein and plasmid DNA through the cell membranes of human prostate cancer cells and rat gliosarcoma cells using this technique. Calcein uptake was seen in 90 percent of the cells at laser levels that left more than 90 percent of the cells alive.

"We could get almost all of the cells to take up these molecules that normally wouldn't enter the cells, and almost all of the cells remained alive," said Prerona Chakravarty, the study's lead author. "Our laser-activated carbon nanoparticle system enables controlled bubble implosions that can disrupt the cell membranes just enough to get the molecules in without causing lasting damage."

To assess how long the holes in the cell membrane remained open, the researchers left the simulated therapeutics out of the fluid when the cells were exposed to the laser light, then added the agents one second after turning off the laser. They saw almost no uptake of the molecules, suggesting that the cell membranes resealed themselves quickly.

To confirm that the carbon-steam reaction was a critical factor driving the nanoblasts, the researchers substituted gold nanoparticles for the carbon nanoparticles before exposure to laser light. Because they lacked the carbon needed for reaction, the gold nanoparticles produced little uptake of the molecules, Prausnitz noted.

Similarly, the researchers substituted carbon nanotubes for the carbon nanoparticles, and also measured little uptake, which they explained by noting that the nanotubes are less reactive than the carbon black particles.

Experimentation further showed that DNA introduced into cells through the laser-activated technique remained functional and capable of driving protein expression. When plasmid DNA that encoded for luciferase expression was introduced into the cancer cells, production of luciferase increased 17-fold.

For the future, the researchers plan to study use of a less expensive nanosecond laser to replace the ultrafast femtosecond instrument used in the research. They also plan to optimize the carbon nanoparticles so that nearly all of them are consumed during the exposure to laser light. Leftover carbon nanoparticles in the body should produce no harmful effects, though the body may be unable to eliminate them, Prausnitz noted.

"This is the first study showing proof of principle for laser-activation of reactive carbon nanoparticles for drug and gene delivery," he said. "There is a considerable path ahead before this can be brought into medicine, but we are optimistic that this approach can ultimately provide a new alternative for delivering therapeutic agents into cells safely and efficiently."

The full article can be found on the ScienceDaily website at : http://www.sciencedaily.com/releases/2010/07/100727201526.htm

Screening DNA Molecules Through Graphene Nanopores

Nanotechnology continues to revolutionize many fields of medical science - the most recent revolution occuring in the field of genetics. In the following article published online at ScienceDaily, reporters describe how scientists have been able to discover a new way to screen DNA - through graphene nanopores! This technology could certainly help genetics in many areas - such as making reading a DNA sequence much easier, faster and convenient.

Here is the full article:

"ScienceDaily, July 12, 2010 - A team of researchers from Delft University of Technology announces a new type of nanopore devices that may significantly impact the way we screen DNA molecules, for example to read off their sequence. In a paper entitled 'DNA Translocation through Graphene Nanopores' (published online in Nano Letters), they report a novel technique to fabricate tiny holes in a layer of graphene (a carbon layer with a thickness of only 1 atom) and they managed to detect the motion of individual DNA molecules that travel through such a hole.

There is a worldwide race to develop fast and low-cost strategies to sequence DNA, that is, to read off the content of our genome. Particularly promising for the next generation of sequencing are devices where one measures on single molecules. Imagine a single DNA molecule from one of your cells (3 billion bases, 1 meter long if you would stretch it from head to tail) that is read -- base per base -- in real time while sliding between two of your fingers. This is what postdoc dr. Gregory Schneider in the group of professor Cees Dekker and colleagues from the Kavli Institute of Nanoscience have in mind. They now demonstrated a first step in that direction: To slide a single molecule of DNA through a tiny nanoscale hole made in the thinnest membrane that nature can offer, a 1-atom thin layer of graphene.
(Image: Artistic rendering of A DNA molecule traversing through a small hole made in an atomically thin layer of graphene that is located on a Si/SiN chip. (Credit: Image courtesy Cees Dekker lab TU Delft / Tremani)

Graphene is a unique and very special material, and yet widely available: Everyone has graphene at home: graphite is made of layers of graphene and occurs in for example the carbon of pencils, charcoal, or candle soot. But in this research, graphene is used because of that special property that one can make single-atom-thin monolayers of graphene. Why is such an ultrathin membrane important? Let's go back to that wire sliding between your fingers. The distance between two bases in DNA is very small, about half a nanometer, which is 100000 times smaller than the width of a human hair! To read off each base along the DNA, one therefore needs a recorder that is smaller than that half nanometer. If your fingers can be scaled down to that size, you are in business. And here's where these atomically thin graphene membranes are crucial.

What Schneider and coworkers did was to fabricate a nanometer-scale hole -- called a nanopore -- in the graphene membrane, which represents the ideal recorder. They demonstrated that single molecules of DNA in water can be pulled through such a graphene nanopore and, importantly, that each DNA molecule can be detected as it passes through the pore. The detection technique is very simple: upon applying an electrical voltage across the nanopore, ions in the solution start to flow through the hole and a current is detected. This current gets smaller whenever a DNA molecule enters the nanopore and partly blocks the flow of ions. Each single DNA molecule that slides through the pore is thus detected by a drop in the current.

The DNA moves base per base through the nanopore. With the atomically thin graphene nanopore one in principle has the potential for reading off the DNA sequence, base per base. A number of groups worldwide have been trying to realize graphene nanopores. Schneider et al are the first to report their results.

DNA translocation through nanopores has been developed before by the Dekker lab and others, for example using SiN membranes. Graphene nanopores offer new opportunities -- many more than sequencing. Since graphene, unlike SiN, is an excellent conductor, an obvious next step is using the intrinsic conductive properties of graphene. Nanopores offer a range of opportunities of sensors for science and applications".

To view the original article, visit http://www.sciencedaily.com/releases/2010/07/100710101019.htm

"Seeing A Bionic Eye on Medicine's Horizon" With Nanomedical Technology

ScienceDaily (Apr. 21, 2010) — Television's Six Million Dollar Man foresaw a future when man and machine would become one. New research at Tel Aviv University is making this futuristic "vision" of bionics a reality.

Prof. Yael Hanein of Tel Aviv University's School of Electrical Engineering has foundational research that may give sight to blind eyes, merging retinal nerves with electrodes to stimulate cell growth. Successful so far in animal models, this research may one day lay the groundwork for retinal implants in people.

But that's a way off, she says. Until then, her half-human, half-machine invention can be used by drug developers investigating new compounds or formulations to treat delicate nerve tissues in the brain. Prof. Hanein's research group published its work recently in the journal Nanotechnology.

The image above shows two rat neuronal cells bound

to a rough carbon nanotube mat. (Credit: AFTAU)

Implanting the idea


"We're working to interface man-made technology with neurons," says Prof. Hanein. "It can be helpful in in vitro and in in vivo applications, and provides an understanding of how neurons work so we can build better devices and drugs," she says.


She's developed a spaghetti like mass of nano-sized (one-millionth of a millimetre) carbon tubes, and using an electric current has managed to coax living neurons from the brains of rats to grow on this man-made structure. The growth of living cells on the nano substrate is a very complicated process, she says, but they adhere well to the structure, fusing with the synthetic electrical and physical interface. Using the new technology developed in Prof. Hanein's laboratory, her graduate student Mark Shein has been observing how neurons communicate and work together.

"We are attempting to answer very basic questions in science," Prof. Hanein explains. "Neurons migrate and assemble themselves, and using approaches we've developed, we are now able to 'listen' to the way the neurons fire and communicate with one another using electrical impulses. Listening to neurons 'talking' allows us to answer the most basic questions of how groups of nerves work together. If we can investigate functional neuronal networks in the lab, we can study what can't be seen or heard in the complete brain, where there are too many signals in one place."


Paging Steve Austin


One application of Prof. Hanein's research is a new approach to aid people with retinal degeneration diseases. There are several retinal diseases which are incurable, such as retinitis pigmentosa, and some researchers are investigating a prosthetic device which could replace the damaged cells.

"Neurons like to form good links with our special nanotechnology, and we're now investigating applications for retinal implants," says Prof. Hanein. "Our retinal implant attempts to replace activity in places of the damaged cells, and in the case of retinal diseases, the damaged photoreceptors."

The team's major breakthrough is creating these man-made living "devices" on a flexible nano-material suited for the small area in the eye where new neuron connection growth would be needed. This is the first step in a long clinical process that may lead to improved vision ― and perhaps, one day, a real-life six million dollar man.

- From http://www.sciencedaily.com/.
For the original article, visit http://www.sciencedaily.com/releases/2010/03/100322143221.htm

Carbon Nanostructures: Elixir or Poison?

ScienceDaily (Apr. 1, 2010) — A Los Alamos National Laboratory toxicologist and a multidisciplinary team of researchers have documented potential cellular damage from "fullerenes" -- soccer-ball-shaped, cage-like molecules composed of 60 carbon atoms. The team also noted that this particular type of damage might hold hope for treatment of Parkinson's disease, Alzheimer's disease, or even cancer.

The research recently appeared in Toxicology and Applied Pharmacology and represents the first-ever observation of this kind for spherical fullerenes, also known as buckyballs, which take their names from the late Buckminster Fuller because they resemble the geodesic dome concept that he popularized.

Engineered carbon nanoparticles, which include fullerenes, are increasing in use worldwide. Each buckyball is a skeletal cage of carbon about the size of a virus. They show potential for creating stronger, lighter structures or acting as tiny delivery mechanisms for designer drugs or antibiotics, among other uses. About four to five tons of carbon nanoparticles are manufactured annually.

"Nanomaterials are the 21st century revolution," said Los Alamos toxicologist Rashi Iyer, the principal research lead and coauthor of the paper. "We are going to have to live with them and deal with them, and the question becomes, 'How are we going to maximize our use of these materials and minimize their impact on us and the environment?'"

Iyer and lead author Jun Gao, also a Los Alamos toxicologist, exposed cultured human skin cells to several distinct types of buckyballs. The differences in the buckyballs lay in the spatial arrangement of short branches of molecules coming off of the main buckyball structure. One buckyball variation, called the "tris" configuration, had three molecular branches off the main structure on one hemisphere; another variation, called the "hexa" configuration, had six branches off the main structure in a roughly symmetrical arrangement; the last type was a plain buckyball.

The researchers found that cells exposed to the tris configuration underwent premature senescence -- what might be described as a state of suspended animation. In other words, the cells did not die as cells normally should, nor did they divide or grow. This arrest of the natural cellular life cycle after exposure to the tris-configured buckyballs may compromise normal organ development, leading to disease within a living organism. In short, the tris buckyballs were toxic to human skin cells.

Moreover, the cells exposed to the tris arrangement caused unique molecular level responses suggesting that tris-fullerenes may potentially interfere with normal immune responses induced by viruses. The team is now pursuing research to determine if cells exposed to this form of fullerenes may be more susceptible to viral infections.

Ironically, the discovery could also lead to a novel treatment strategy for combating several debilitating diseases. In diseases like Parkinson's or Alzheimer's, nerve cells die or degenerate to a nonfunctional state. A mechanism to induce senescence in specific nerve cells could delay or eliminate onset of the diseases. Similarly, a disease like cancer, which spreads and thrives through unregulated replication of cancer cells, might be fought through induced senescence. This strategy could stop the cells from dividing and provide doctors with more time to kill the abnormal cells.

Because of the minute size of nanomaterials, the primary hazard associated with them has been potential inhalation -- similar to the concern over asbestos exposure.

"Already, from a toxicological point of view, this research is useful because it shows that if you have the choice to use a tris- or a hexa-arrangement for an application involving buckyballs, the hexa-arrangement is probably the better choice," said Iyer. "These studies may provide guidance for new nanomaterial design and development."

These results were offshoots from a study (Shreve, Wang, and Iyer) funded to understand the interactions between buckyballs and biological membranes. Los Alamos National Laboratory has taken a proactive role by initiating a nanomaterial bioassessmnet program with the intention of keeping its nanomaterial workers safe while facilitating the discovery of high-function, low-bioimpact nanomaterials with the potential to benefit national security missions. In addition to Gao and Iyer, the LANL program includes Jennifer Hollingsworth, Yi Jiang, Jian Song, Paul Welch, Hsing Lin Wang, Srinivas Iyer, and Gabriel Montaño.

Los Alamos National Laboratory researchers will continue to attempt to understand the potential effects of exposure to nanomaterials in much the same way that Los Alamos was a worldwide leader in understanding the effects of radiation during the Lab's early history. Los Alamos workers using nanomaterials will continue to follow protocols that provide the highest degree of protection from potential exposure.

Meantime, Los Alamos research into nanomaterials provides a cautionary tale for nanomaterial use, as well as early foundations for worker protection. Right now, there are no federal regulations for the use of nanomaterials. Disclosure of use by companies or individuals is voluntary. As nanomaterial use increases, understanding of their potential hazards should also increase.

~ Taken from http://www.sciencedaily.com/

The article can also be accessed at http://www.sciencedaily.com/releases/2010/03/100331151146.htm

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A Revolution in the Battle Against Cancer!!!!

Nanotech cancer treatment shown to work in humans

Nanotechnology has been generating a lot of excitement in the cancer research community. Scientists at institutions worldwide have gotten involved in looking at how tiny particles, specially designed to target cancer in the body and treat it, might work better than taking a regular drug. That's because targeted therapies would not harm healthy cells, reducing the toxic side effects seen in chemotherapy drugs.

After decades of work in animal models, there is now evidence that the approach works in humans. A paper published Sunday in the journal Nature shows that nanoparticles can successfully home to proteins associated with cancer progression, deliver medication, and turn off those proteins.


This is the first study to show that this particular method, using a mechanism called RNA interference, works in humans, said Gayle Woloschak, professor of radiology, and cell and molecular biology, at Northwestern University, who was not involved in the study.


But the study, led by Mark Davis at California Institute of Technology, is preliminary. It looked at three patients with melanoma, a form of skin cancer. Because only one of the patients consented to the biopsies due to all of the analysis, the researchers have conclusive evidence that the therapy – and not any previous treatment the patient may have had – was responsible for reducing the cancer-related protein in that patient, Davis said.

But the study showed targeting – that the nanoparticles got inside the tumor cells – in all three patients, Davis said. The more nanoparticles sent into the body, the more of these tiny structures get into the tumor cells, he said.


Although this is a small sample of participants, the study is still very important to show how the new technology works in humans, Woloschak said.


Particles used in this study were about 70 nanometers across, smaller than most viruses, Woloschak said. The therapy was injected directly into the patients' bloodstreams.


Researchers also demonstrated that a large number of different materials can be put together by using nanoparticles as scaffolds. This study used a tumor targeting agent and an anti-cancer therapy, but future possibilities include an imaging agent "so that a tumor can be observed as it is progressing through therapy," she said.


Results from the clinical trial associated with Davis' study will be presented at the meeting of the American Society of Clinical Oncology in June.

Largely, the idea of targeted nanoparticles as cancer treatments has been shown to work in animals, but not humans. Last year CNNHealth reported on the buzz on "nanobees," which use this method, as well as other concepts in the works. Read more about that here: http://www.cnn.com/2009/HEALTH/08/18/nanotech.cancer.nano.tumors/index.html

~ Taken from Dr. Sanjay Gupta's Blog (CNN)