Cells are very good at protecting their precious contents -- and as a result, it's very difficult to penetrate¹ their membrane² walls to deliver drugs, nutrients³ or biosensors without damaging or destroying the cell. One effective way of doing so, discovered in 2008, is to use nanoparticles of pure gold, coated with a thin layer of a special polymer. But nobody knew exactly why this combination worked so well, or how it made it through the cell wall. Now, researchers at MIT and the Ecole Polytechnique de Lausanne in Switzerland have figured out how the process works, and the limits on the sizes of particles that can be used. Their analysis appears in the journal Nano Letters, in a paper by graduate students Reid Van Lehn, Prabhani Atukorale, Yu-Sang Yang and Randy Carney and professors Alfredo Alexander-Katz, Darrell Irvine and Francesco Stellacci.

 

Until now, says Van Lehn, the paper's lead author, "the mechanism⁴ was unknown. … In this work, we wanted to simplify the process and understand the forces" that allow gold nanoparticles to penetrate cell walls without permanently⁵ damaging the membranes⁶ or rupturing⁷ the cells. The researchers did so through a combination of lab experiments and computer simulations.

 

The team demonstrated that the crucial first step in the process is for coated gold nanoparticles to fuse with the lipids -- a category of natural fats, waxes and vitamins -- 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 applied⁸ to the gold particles consists of a mix of hydrophobic and hydrophilic components⁹ that form a monolayer -- a layer just one molecule¹⁰ thick -- on the particle's surface. Any of several different compounds can be used, the researchers explain.

 

"Cells tend to engulf¹¹ things on the surface," says Alexander-Katz, an associate professor of materials science and engineering at MIT, but it's "very unusual" for materials to cross that membrane into the cell's interior without causing major damage. Irvine and Stellacci demonstrated in 2008 that monolayer-coated gold nanoparticles could do so; they have since been working to better understand why and how that works.

 

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, the researchers say. However, there is some evidence that the gold particles have therapeutic¹² properties, which could be a side benefit.

 

Gold particles are also very good at capturing X-rays -- so if they could be made to penetrate cancer cells, and were then heated by a beam of X-rays, they could destroy those cells from within. "So the fact that it's gold may be useful," says Irvine, a professor of materials science and engineering and biological engineering and member of the Koch Institute for Integrative Cancer Research.

 

Significantly, the mechanism that allows the nanoparticles to pass through the membrane seems also to seal the opening as soon as the particle has passed. "They would go through without allowing even small molecules¹³ to leak through behind them," Van Lehn says.

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