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