Abstract

With the capability to specific silence target gene expression, RNA interference (RNAi) technology has emerged as a powerful tool for cancer treatment. Although diversified delivery platforms have been designed for siRNA-based gene therapy, few delivery systems could fulfill all the requirements during the delivery process in vivo. Here, a nano-scale quaternary polyplex (NQP) that can optimize the entire process of tumor-targeted siRNA delivery from intravenous injection to gene silencing inside cells is proposed. NQP is endowed with a core–shell structure composed of an siRNA loaded, ATP-responsive core and a pH-responsive shell. This unique structure enables NQP to achieve optimal efficiency in all essential steps during the siRNA delivery, including blood circulation, tumor accumulation, cell internalization, and controlled release of siRNA. As a result, administration of siSTAT3-loaded NQP to tumor-bearing mice achieved efficient gene silencing and tumor growth inhibition. Since siSTAT3 could be replaced by any siRNA, NQP could become a promising platform for the development of siRNA-based cancer gene therapy.

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