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Nanoparticle Co-delivery of RNAi and Chemotherapy for Multidrug Resistant Cancers

Jinjun Shi

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National Institutes of Health (NIH)
A critical barrier to effective cancer chemotherapy is the development of multidrug resistance(MDR) in cancer cells. The broad and long-term objective of this project is to develop advancednanomedicinal approaches for the treatment of multidrug resistant cancers. We believe thatnanomedicinal therapy, which can simultaneously deliver RNAi therapeutics to suppress MDR andchemotherapeutic agents to induce the death of cancer cells, will be of particular interest inaddressing the challenge of MDR in cancer chemotherapy. Specifically, we will design and developnanoparticulate platforms for the effective co-delivery of RNAi and anti-cancer agents with asynergistic drug ratio to taxane-resistant lung and prostate cancer cells, by using biodegradable andbiocompatible polymers and lipids. The contribution of different drug-resistant proteins to cancerMDR will be compared. The physicochemical properties of the nanoparticles will also be optimized toovercome the physiological barriers in vivo, while keeping the co-delivery of RNAi and chemotherapysafe and effective. Furthermore, in the R00 independent phase, the nanoparticulate platform will beprecisely engineered to control the temporal release of individual agents and to achieve targeted drugdelivery. We hypothesize that the spatiotemporal controlled delivery of nanotherapeutics canmaximize the desired effects of RNAi and anti-cancer agents for multidrug resistant cancers, whileminimizing their toxic side effects. If successful, this project will lay the groundwork for widerapplications of the nanotechnology-based targeted combination therapy for cancer and otherdiseases.

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