Shape, Not Just Size, Impacts Effectiveness of Nanotherapeutics
In the budding field of nanotechnology, scientists already know that size does matter. But now, investigators at The University of North Carolina at Chapel Hill (UNC) have shown that shape matters even more. A team of researchers led by Joseph DeSimone, Ph.D., a member of the Carolina Center of Cancer Nanotechnology Excellence, has demonstrated that nanoparticles designed with a specific shape, size, and surface chemistry are taken up into cells and behave differently within cells depending on these attributes. Their findings appear in the Proceedings of the National Academy of Sciences of the United States of America.
Previous studies have shown that drug-carrying nanoparticles can home in on and attack tumors, in part because of their extremely small size, which allows them to pass through cell membranes. However, up until now, existing techniques have meant that targeting agents could be delivered only by using spherical- or granular-shaped particles.
Using PRINT® (Particle Replication in Non-wetting Templates) technology, a technique invented in Dr. DeSimone’s lab that allows scientists to design and produce “custom-made” nanoparticles, the UNC researchers made particles with specific shapes, sizes, and surface charges. Dr. DeSimone said that the aim is to optimize particle attributes for specific therapeutic objectives. “This would mean that we could deliver lower dosages of drugs to specific cells and tissues in the body and actually be more effective in treating the cancer,” he said.
Creating particles of different dimensions, the UNC researchers changed one variable at a time and experimented with different surface chemistries. They then incubated the different particles with human cervical carcinoma epithelial cells, monitoring each type to see which ones the cells absorbed most effectively. For instance, the scientists discovered that long, rod-shaped particles (diameter, 150 nanometers [nm]; height, 450 nm) were internalized by cells approximately 4 times faster than lower-aspect ratio particles (diameter, 200 nm; height, 200 nm) and traveled significantly farther into the cells.
This work, which appears in the paper “The Effect Of Particle Design On Cellular Internalization Pathways,” was supported by the NCI Alliance for Nanotechnology in Cancer. An abstract of this paper is available at the journal’s Web site.