Intracellular Nanoparticle Aggregation as a Mechanism for Inducing Apoptosis in Breast Cancer Cells

Abstract : The current paradigm of drug delivery using nanotechnology has been focused on coupling chemotherapeutic molecules to nanoparticulate delivery systems. In this work, we propose that pH-triggered aggregation alone of nanoparticles (that are non-toxic when not aggregated) can induce death in breast cancer cells. We hypothesize that non-toxic, protein nanoparticles, when internalized by endocytosis and triggered to aggregate inside breast cancer cells, will be cytotoxic to them. We will examine (a) the extent to which pH-induced intracellular aggregation is cytotoxic, and (b) whether coupling a chemotherapeutic drug to a pH-responsive protein nanoparticle yields synergistic effects on the toxicity. Although this was a Concept Award which only funded one year of proposed research, a one-year, no-cost extension has been granted to complete the remaining tasks. This current report reflects the one-year update report.