Abstract
Nanotechnology has introduced many exciting new tools for the treatment of human diseases. One of the obstacles in its application to that end is the lack of a fundamental understanding of the interaction that occurs between nanoparticles and living cells. This report describes the quantitative analysis of the kinetics and endocytic pathways involved in the uptake of anatase titanium dioxide (TiO(2)) nanoparticles into prostate cancer PC-3M cells. The experiments were performed with TiO(2) nanoconjugates: 6-nm nanoparticles with surface-conjugated fluorescent Alizarin Red S. Results obtained by flow cytometry, fluorescence microscopy, and inductively coupled plasma-mass spectrometry confirmed a complex nanoparticle-cell interaction involving a variety of endocytic mechanisms. The results demonstrated that a temperature, concentration, and time-dependent internalization of the TiO(2) nanoparticles and nanoconjugates occurred via clathrin-mediated endocytosis, caveolin-mediated endocytosis, and macropinocytosis. FROM THE CLINICAL EDITOR: The interaction and uptake of TiO(2) nanoparticles (6-nm) with prostate PC-3M cells was investigated and found to undergo temperature, time, and concentration dependent intracellular transport that was mediated through clathrin pits, caveolae, and macropinocytosis. These results suggest that nanoparticles may widely permeate through tissues and enter almost any active cell through a variety of biological mechanisms, posing both interesting opportunity and possible challenges for systemic use.