A Tailored DNA Nanoplatform for Synergistic RNAi‐/Chemotherapy of Multidrug‐Resistant Tumors

Abstract

Multidrug resistance (MDR) is a major obstacle in the clinical treatment of cancer. Herein, a facile strategy is reported to construct a versatile DNA nanostructure as a co-delivery vector of RNA interference (RNAi) and chemodrugs to combat multidrug-resistant tumor (MCF-7R) in vitro and in vivo. In the tailored nanocarrier, two linear small hairpin RNA (shRNA) transcription templates targeting MDR-associated genes (gene of P-glycoprotein, a typical drug efflux pump; and gene of survivin, a representative anti-apoptotic protein) are precisely organized in the chemodrug (doxorubicin, DOX) pre-loaded DNA origami. With the incorporation of active targeting and controlled-release elements, these multifunctional DNA nanocarriers can successfully enter the target MCF-7R cells and synergistically inhibit tumor growth without apparent systemic toxicity. This tailored DNA nanoplatform, which combines RNAi therapy and chemotherapy, provides a new strategy for the treatment of multidrug-resistant tumors.