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MIT researchers find gold nanoparticle standard for cell penetration
CAMBRIDGE, Mass.— In a paper recently published in Nano Letters, an international research team comprised of scientists from the Massachusetts Institute of Technology (MIT) and the Ecole Polytechnique de Lausanne in Switzerland offer their finding that gold nanoparticles with special coatings can deliver drugs or biosensors to a cell's interior without damaging it.
Scientists have long wrestled with the inability to penetrate cells' membrane walls to deliver drugs, nutrients or biosensors without damaging or destroying the cell. In 2008, researchers at MIT devised a way to accomplish this using nanoparticles of pure gold, coated with a thin layer of a special polymer. With little understanding of how these particles penetrated the cell wall, the MIT-Swiss team set out to understand why this process works and the limits on the sizes of particles that can be used.
"In 2008, all we knew is that when we synthesized particles, some would go into the cell and some would not, and we didn't know why," says Reid Van Lehn, a graduate student at MIT and a co-author on the paper. "The mechanism was not understood at all. It was just an observation, essentially. We wanted to be able to understand the design rules associated with bypassing this membrane so we can develop a new generation of therapeutics that can enter the cell."
The international team did so using a combination of lab experiments and computer simulations. First, the team demonstrated that the crucial first step in the process is for coated gold nanoparticles to fuse with the lipids that form the cell wall. The scientists also demonstrated an upper limit on the size of such particles that can penetrate the cell wall—a limit that depends on the composition of the particle's coating. The coating applied to the gold particles consisted of a mix of hydrophobic and hydrophilic components that form a monolayer—a layer just one molecule thick—on the particle's surface.
Any of several different compounds can be used, according to the researchers. Since the nanoparticles themselves are completely coated, the fact that they are made of gold doesn't have any direct effect, except that gold nanoparticles are an easily prepared model system. However, there is some evidence that the gold particles have therapeutic properties, which could be a side benefit, according to the team. In addition, the researchers observed that the mechanism which allows the nanoparticles to pass through the membrane also seems to seal the opening as soon as the particle has passed.
"They would go through without allowing even small molecules to leak through behind them," Van Lehn says.
There are many potential drug development applications that could arise from these findings, says Van Lehn. First, because gold particles are good at capturing X-rays, they could be made to penetrate cancer cells and destroy them from within.
"Our major goal is working toward the idea of minimalizing the harmful side effects of chemotherapy," says Van Lehn.
If the coatings can be targeted to a particular cell type that is the target of a drug, that could also give drug developers a significant leg up in first-in-class drug development. Another potential application could be in attaching or inserting biosensing molecules on or into certain cells, enabling scientists to detect or monitor specific biochemical markers such as proteins that indicate the onset or decline of a disease or a metabolic process.
"If we can combine our mechanism with one targeting specific cells, that would be the holy grail of drug development," Van Lehn notes. "We think there is a lot of potential here, and we are actively looking to follow that up."
The paper, "Effect of Particle Diameter and Surface Composition on the Spontaneous Fusion of Monolayer-Protected Gold Nanoparticles with Lipid Bilayers," was published online Aug. 5 in Nano Letters, an American Chemical Society publication. Other authors on the paper include graduate students Prabhani Atukorale, Yu-Sang Yang and Randy Carney, and professors Alfredo Alexander-Katz, Darrell Irvine and Francesco Stellacci.