(373e) Effects of Chemotherapeutic Mediators On Intracellular Trafficking of Nanoparticles

Nanoparticles have been investigated as therapeutics and imaging agents for a variety of diseases, including cancer. However, the efficacy of these therapeutics and imaging agents is often compromised by various resistance mechanisms at the cellular level. We report an investigation into intracellular transport and sub-cellular localization of nanoparticles in cancer cells with an eye towards enhancing their efficacies. In addition to nanoscale polymer:DNA complexes, quantum dots (QDs) were used as model nanoparticles because of their high brightness and photostability. We demonstrate that even in closely related human prostate cancer cell lines, differences in cell phenotype led to dramatically different intracellular localization behavior of nanoparticles. Quantum dots and polymer-DNA complexes were distributed throughout the cytoplasm in PC3 prostate cancer cells while they were internalized by clathrin-mediated endocytosis, trafficked along microtubules, and localized at the perinuclear recycling compartments (PNRC) in PC3-PSMA cells (sub-clones of PC3 cells retrovirally transduced to stably express PSMA receptors). Chemotherapeutic mediators of intracellular trafficking, including histone deacetylase inhibitors (e.g. tubacin and trichostatin A) and mediators of cell cycle progression were investigated in order to modulate nanoparticle trafficking and localization inside cells. This investigation has led to a better understanding of how cancer cells process nanoparticles and has resulted in novel methods for overcoming cellular resistances associated with nanoscale therapeutics and imaging agents.