Clusterization of nanoparticles during their interaction with living cells

Aims: Clusters of nanoparticles may significantly improve the sensitivity of diagnostics and the safety and efficacy of therapeutic nanotechnologies in medicine. We report methods for the formation of nanoparticle clusters and for monitoring their accumulation in cancer cells. Methods: The accumulation of gold nanoparticles in tumor cells was studied using flow cytometry, optical scattering and fluorescent, atomic force, photothermal and scanning electron microscopy. Results: Incubation of cells at 37 degrees C for 30 min or more with 10-30-nm nanoparticles resulted in the formation of clusters of nanoparticles as large as 20 nanoparticles or more. Conclusions: Specific targeting using a monoclonal antibody as a vector increases the concentration of nanoparticles on the surface of target cells compared with nonspecific nanoparticle accumulation. In turn, an increased concentration of nanoparticles on the target surface yields larger nanoparticle clusters inside the cells due to endocytosis. Photothermal and scattering microscopy were found to be the most sensitive methods for imaging nanoparticle clusters in living cells.