Researchers from Michigan State University in East Lansing Monday announced they have created a computer simulation to help design drug-delivery nanoparticles that carry cancer-fighting medicines directly to tumors while minimizing the potential side effects on healthy cells.
MSU is working with Stanford University in California. Bryan Smith, associate professor in MSU’s College of Engineering, and Eric Shaqfeh, professor at Stanford, published their findings in a recent issue of Biophysics Journal.
Previous research shows drugs embedded in nanoparticles are generally better able to evade biological barriers than free-roaming drug molecules. However, nanoparticles have shown limited success in reaching their targets. The critical roadblock has been getting the drug from the bloodstream into the tumor.
In the study, researchers sought to identify the optimal shape for nanoparticles to act as a molecular carrier to get small-molecule drugs out of the blood vessels and into the interstitial fluids that bathe the tumor. This is where the drugs can enter cancerous cells. Once inside, the nanoparticles dissolve, allowing the drug molecules to kill the tumor cells.
“There has been little previous mechanistic understanding of how nanoparticle transport occurs at the nanoscale, and thus, also how to select the physical properties of a nanoparticle for targeting a patient’s tumor,” says Smith. “Nanoparticles have been used as superior delivery agents, but, so far, even nanoparticles have shown limited success in reaching their targets. Prior attempts at understanding the extravasation process of nanoparticles via theory/simulation have not accounted for the shape of nanoparticles.
“In our work, we bridged this and other gaps, developing a full-fledged simulation of the extravasation of particles of arbitrary shape, connected with validating experimental studies which allowed us to study the effect of particle shape and size on extravasation ability.”
The nanoparticle delivery method exploits the haphazard way in which tumors grow. Cancers are hastily assembled piles of cells with porous blood vessels. Cancer-killing drugs can enter the tumor through the pores.
Simulations and experiments the researchers completed showed how nanoparticles of different shapes flow through blood vessels, go through the pores, and reach cancer cells. Because cancers can be different, the shapes and sizes of nanoparticle delivery systems may have to be tailored to the specific tumor. The researchers say their model will help drug designers accurately predict the optimal particle shape and size to most effectively treat the tumor. Previous models oversimplified nanoparticle shapes.
Through experiments, the team found that long, thin particles typically go through the pores best. The researchers also learned that the process of diffusion, through which particles move from areas of higher to lower concentration, is a factor in whether nanoparticles will go through pores.
Smith and Shaqfeh hope to explore how the polymers that make the nanoparticles more biocompatible control their delivery properties. They also plan to broaden their models to include electrical forces that might cause pores to attract or repel nanoparticles.
