(119a) Synergistic Subcellular Targeting By Shape-Engineered Nanoparticles

The efficiency of drug nanoparticles depends not only on their known biological functions, but also on their ability to bind to the target cell membrane, and being internalized into right cellular compartments without causing undesirable side effects. While it has been shown that nanoparticle properties such as size, shape and surface charge affect their binding, uptake and lysosomal rupture for effective therapeutic actions, however, insights of synergistic targeting of multiple subcellular compartments using shape specific single drug nanoparticles have not been explored. Here, we describe the preparation of rod-shape drug nanoparticles that simultaneously target cell membrane, endosome and nucleus of cancer cells to inhibit cancer cell growth synergistically. Our recent study showed how nanoparticle shape modulated cell membrane targeting and uptake by enhancing multivalent interactions of rod-shaped nanoparticles than spherical nanoparticles with the cell membrane. In this study, we investigate how synergistic targeting of cell surface, endosome and nucleus by rod-shaped drug nanoparticles regulates a balance of internalization and recycling rates, and thus enhances the therapeutic efficiency at very low drug concentrations. The results are important for the rational design of drug nanoparticles to maximize their sub-cellular distribution for effective therapeutic actions at the target site.