Shedding light on how nanoparticles enter cells

Nanoparticles are a promising tool for treating a wide range of diseases like cancer and stroke. A new University of Georgia study sheds light on how their properties could facilitate the delivery of drugs and other therapies.

Mechanical engineer Xianqiao Wang led a team that used computational modeling to explore the combined effects of shape and stiffness of nanoparticles, factors that impact transportation of the particles via blood flow, as well as cells’ ability to take nanoparticles inside the cell, known as endocytosis.

“It’s still challenging to observe this type of dynamic process—how a nanoparticle gets inside a cell—through experimental observation,” said Wang, associate professor in the College of Engineering. “The nanoscale in both length and time is tiny, and the process is not easy to capture. Modeling and simulation provide a window for reproducing and capturing this process.”

For the study, published in the Journal of Physical Chemistry B, the team modeled spherocylindrical, rod-shaped nanoparticles that varied in aspect ratio and stiffness.

“In nature, there are a lot of viruses that are a long rod shape,” Wang said. “These kinds of viruses have a very active motion with cells and can easily get inside.”

Stiffness affects how easily the nanoparticle can be taken in by a cell and what happens afterward. A short and stiff nanoparticle easily penetrates a cell’s membrane but may remain intact inside the cell, making it difficult to release the therapy being delivered.

With a long and soft nanoparticle, the cell’s membrane can bend the nanoparticle into a “u” or “v” shape as it brings the nanoparticle inside—possibly offering a mechanism for releasing a drug.

“Maybe this bending mode can trigger the drug release,” Wang said. “That’s an interesting point for future research—to find a way to release the drug when it’s carried by a nanoparticle.”

Results of the study indicate that the time required for a cell’s uptake of a nanoparticle increases as the nanoparticle’s size increases. In addition, soft and long nanoparticles exhibited wormlike wiggling—in contrast to the rod-like penetration of stiff nanoparticles—enlarging the contact area and facilitating endocytosis.

The team also explored, for the first time, how an imperfect or damaged membrane affects endocytosis. When a membrane is partially damaged, it actually facilitates the process of bringing ­the nanoparticle into the cell, according to Wang. Extra time is needed to heal the membrane defect, however, so the cell won’t die.

These findings provide information for experimental scientists to build on.

“Our deeper understanding of nanoparticle endocytosis will be a useful guideline for designs that can be implemented in next-generation, nanoparticle-assisted therapy,” Wang said. “There are many potential applications, from chemical therapy that uses a nanoparticle vehicle to target a certain type of cancer cells, to personalized medicine that creates nanoparticles with specific functions for a particular patient.”

By Allyson Mann

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