DeSimone also identified the precise mechanisms by which cells take in particles of different shapes. These mechanisms determine where the particles end up inside the cell. This new data could help researchers design particles that reach particular compartments within a cell that have a known level of acidity. The researchers could then fine-tune the particles so that they break down and release their cargo only once they reach the desired compartment. That way, the particles will only release drugs inside targeted cells, leaving healthy cells unharmed.
DeSimone is using his manufacturing technique to produce nanoparticles that deliver drugs to cancer cells. He’s starting trials in mice for a number of cancer types–breast, ovarian, cervical, lung, prostate–and lymphoma. He’s able to conduct so many trials because it’s easy to add different treatment molecules to his particles. Particles developed for targeting breast cancer can easily be changed to target lung cancer, for example. During the tests, DeSimone will systematically vary doses, sizes, and so on to determine the least toxic, most effective combinations. “You can now barrage a lot of different cancers and look at what’s the most efficacious design parameters you can put in the system,” he says.
DeSimone has developed particles that resemble red blood cells in size, shape, and flexibility to help them circulate in the bloodstream without being removed by biological barriers. (He’s testing these in animals as a potential basis for artificial blood.) He is also testing long, wormlike particles that can’t easily be consumed by macrophages. “The particle has to overcome so many hurdles before it reaches its destination,” Mitragotri says. Previously, researchers have been limited to changing the size and chemistry of particles. Adding the ability to control shape provides a “big boost in overcoming these hurdles,” Mitragotri says.