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Layer-by-Layer (LbL) nanoparticles for synergistic RNA interference (RNAi) and cancer chemotherapy. Nanoparticles have been systemically administered in humans since clinical approval of the first micellar drug, Sandimmune®, by the US FDA in 1983 and the first polymer-drug nanoconjugate, Adagen®, later in 1990. Despite tremendous improvements in our ability to detect and treat solid tumors afforded by such technologies, current nanomedicinal strategies are typically limited to a singular targeting and/or therapeutic modality. We are developing multifunctional nanoscale platforms for the treatment of solid tumors that selectively target, sensitize, and treat malignant cells. This synergistic strategy relies on the use of polyelectrolyte nanoparticles that preferentially localize at tumor sites and subsequently degrade, delivering small interfering RNA sequences that sensitize cancer cells towards co-delivered chemotherapeutics. We believe that this approach can greatly augment tolerable dosages of active chemotherapeutics and diminish their unintended side-effects in order to realize improved patient health and survival.
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