Striped Nanoparticles Key to Nanoparticle Drug Delivery

In research that could at the same time impact the delivery of drugs and explain a biological enigma, engineers have created the first synthetic nanoparticles that can penetrate a cell without poking a hole in its protective membrane and destroying it.

The team of investigators, from the Massachusetts Institute of Technology (MIT; Cambridge, MA, USA), found that gold nanoparticles coated with alternating bands of two different types of molecules could quickly pass into cells without harming them, while those randomly coated with the same materials cannot. The research was reported in a May 25, 2008, advance online publication of the journal Nature Materials.

"We've created the first fully synthetic material that can pass through a cell membrane without rupturing it, and we've found that order on the nanometer scale is necessary to provide this property,” said Dr. Francesco Stellacci, an MIT associate professor in the department of materials science and engineering and coleader of the study with Dr. Darrell Irvine, an MIT associate professor of tissue engineering.

In addition to the practical applications of such nanoparticles for drug delivery--the MIT team used them to deliver fluorescent imaging agents to cells; the miniscule spheres could help explain how some biological materials such as peptides are able to enter cells. "No one understands how these biologically derived cell-penetrating materials work,” said Dr. Irvine. "So we could use the new particles to learn more about their biological counterparts. Could they be analogues of the biological system?”

When a cell membrane recognizes a foreign object such as a nanoparticle, it usually wraps around or "devours” it, encasing the object in a smaller bubble inside the cell that can eventually be excreted. Any drugs or other agents attached to the nanoparticle, never reach the main fluid section of the cell, or cytosol, where they could have an effect.

Such nanoparticles can also be "chaperoned” by biologic molecules into the cytosol, but this too has disadvantages. Chaperones can work in some cells but not others, and carry one cargo but not another. Therefore, the importance of the MIT work in developing nanoparticles that can directly penetrate the cell membrane, deliver their cargo to the cytosol, and do so without killing the cell.

Dr. Irvine compares the feat to a phenomenon kids can discover. "If you have a soap film and you poke it with a bubble wand, you'll pop it,” Dr. Stellacci said. "But if you coat the bubble wand with soap before poking the film, it will pass through the film without popping it because it's coated with the same material.” Dr. Stellacci noted that the coated nanoparticles have properties similar to the cell membrane--not identical--but the analogy is still applicable.

Dr. Stellacci first reported the creation of the striped nanoparticles in a 2004 Nature Materials article. At the time, "we noticed that they interacted with proteins in an interesting way,” he said. "Could they also have interesting interactions with cells?” Four years later, he and his colleagues reported a clear "yes.”


Related Links:
Massachusetts Institute of Technology