Tag Archives: Darrell J. Irvine

So, why do gold nanoparticles facilitate cell penetration without damage to cell walls?

Researchers at the Massachusetts Institute of Technology (MIT) and l’École Polytechnique Fédérale de Lausanne (EPFL) in Switerzerland have found an answer to the question about why gold nanoparticles facilitate cell penetration without damage to the cell walls. Apparently it has nothing to with the gold; it’s all in the coating according to an Aug. 23, 2013 MIT news release by David L. Chandler (also on EurekAlert),

Cells are very good at protecting their precious contents — and as a result, it’s very difficult to penetrate their membrane walls to deliver drugs, nutrients 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. …

Until now, says Van Lehn, the paper’s lead author [Reid Van Lehn], “the mechanism was unknown. … In this work, we wanted to simplify the process and understand the forces” that allow gold nanoparticles to penetrate cell walls without permanently damaging the membranes or rupturing the cells. The researchers did so through a combination of lab experiments and computer simulations.

The news release goes on to provide details about the research,

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. [emphases mine]

The coating applied to the gold particles consists 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, the researchers explain. [emphases mine]

“Cells tend to engulf 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 therapeutic 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 molecules to leak through behind them,” Van Lehn says.

Irvine says that his lab is also interested in harnessing this cell-penetrating mechanism as a way of delivering drugs to the cell’s interior, by binding them to the surface coating material. One important step in making that a useful process, he says, is finding ways to allow the nanoparticle coatings to be selective about what types of cells they attach to. “If it’s all cells, that’s not very useful,” he says, but if the coatings can be targeted to a particular cell type that is the target of a drug, that could be a significant benefit.

Another potential application of this work could be in attaching or inserting biosensing molecules on or into certain cells, Van Lehn says. In this way, scientists could detect or monitor specific biochemical markers, such as proteins that indicate the onset or decline of a disease or a metabolic process.

The research paper can be found here,

Effect of Particle Diameter and Surface Composition on the Spontaneous Fusion of Monolayer-Protected Gold Nanoparticles with Lipid Bilayers by Reid C. Van Lehn, Prabhani U. Atukorale, Randy P. Carney, Yu-Sang Yang, Francesco Stellacci, Darrell J. Irvine, and Alfredo Alexander-Katz. Nano Lett., Article ASAP DOI: 10.1021/nl401365n Publication Date (Web): August 5, 2013
Copyright © 2013 American Chemical Society

It is behind a paywall.

DNA tattoo patches

Scientists seem fascinated with tattoos these days (my Dec. 4, 2012 posting, my Nov. 9, 2012 posting, March 20, 2012 posting amongst others). The latest work comes from the Massachusetts Institute of Technology (MIT) according to this Jan. 29, 2013 news item,

In a paper appearing in the Jan. 27 [2013] online issue of Nature Materials (“Polymer multilayer tattooing for enhanced DNA vaccination”), MIT researchers describe a new type of vaccine-delivery film that holds promise for improving the effectiveness of DNA vaccines. If such vaccines could be successfully delivered to humans, they could overcome not only the safety risks of using viruses to vaccinate against diseases such as HIV, but they would also be more stable, making it possible to ship and store them at room temperature.

The Jan. 29, 2013 MIT news release by Anne Trafton, which originated the news item, explains the interest in DNA vaccines and this proposed delivery system,

Vaccines usually consist of inactivated viruses that prompt the immune system to remember the invader and launch a strong defense if it later encounters the real thing. However, this approach can be too risky with certain viruses, including HIV.

In recent years, many scientists have been exploring DNA as a potential alternative vaccine. About 20 years ago, DNA coding for viral proteins was found to induce strong immune responses in rodents, but so far, tests in humans have failed to duplicate that success.

This type of vaccine delivery would also eliminate the need to inject vaccines by syringe, says Darrell Irvine, an MIT professor of biological engineering and materials science and engineering. “You just apply the patch for a few minutes, take it off and it leaves behind these thin polymer films embedded in the skin,” he says.

Scientists have had some recent success delivering DNA vaccines to human patients using a technique called electroporation. This method requires first injecting the DNA under the skin, then using electrodes to create an electric field that opens small pores in the membranes of cells in the skin, allowing DNA to get inside. However, the process can be painful and give varying results, Irvine says.

“It’s showing some promise but it’s certainly not ideal and it’s not something you could imagine in a global prophylactic vaccine setting, especially in resource-poor countries,” he says.

Irvine and Hammond took a different approach to delivering DNA to the skin, creating a patch made of many layers of polymers embedded with the DNA vaccine. These polymer films are implanted under the skin using microneedles that penetrate about half a millimeter into the skin — deep enough to deliver the DNA to immune cells in the epidermis, but not deep enough to cause pain in the nerve endings of the dermis.

Once under the skin, the films degrade as they come in contact with water, releasing the vaccine over days or weeks. As the film breaks apart, the DNA strands become tangled up with pieces of the polymer, which protect the DNA and help it get inside cells.

The researchers can control how much DNA gets delivered by tuning the number of polymer layers. They can also control the rate of delivery by altering how hydrophobic (water-fearing) the film is. DNA injected on its own is usually broken down very quickly, before the immune system can generate a memory response. When the DNA is released over time, the immune system has more time to interact with it, boosting the vaccine’s effectiveness.

The polymer film also includes an adjuvant — a molecule that helps to boost the immune response. In this case, the adjuvant consists of strands of RNA that resemble viral RNA, which provokes inflammation and recruits immune cells to the area.

The ability to provoke inflammation is one of the key advantages of the new delivery system, says Michele Kutzler, an assistant professor at Drexel University College of Medicine. Other benefits include targeting the wealth of immune cells in the skin, the use of a biodegradable delivery material, and the possibility of pain-free vaccine delivery, she says.

Here’s a citation and link to the paper,

Polymer multilayer tattooing for enhanced DNA vaccination by Peter C. DeMuth, Younjin Min, Bonnie Huang, Joshua A. Kramer, Andrew D. Miller, Dan H. Barouch, Paula T. Hammond, & Darrell J. Irvine. Nature Materials (2013) doi:10.1038/nmat3550 Published online 27 January 2013

The article is behind a paywall. And, for those who find images help to better understand,

Graphic: Christine Daniloff/MIT [downloaded from http://web.mit.edu/newsoffice/2013/vaccine-film-delivery-hiv-0127.html]

Graphic: Christine Daniloff/MIT [downloaded from http://web.mit.edu/newsoffice/2013/vaccine-film-delivery-hiv-0127.html]