A Tailored DNA Nanoplatform for Synergistic RNAi-/Chemo- Therapy of Multidrug-Resistant Tumors.

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A Tailored DNA Nanoplatform for Synergistic RNAi-/Chemo- Therapy of Multidrug-Resistant Tumors.

Angew Chem Int Ed Engl. 2018 Oct 04;:

Authors: Liu J, Song L, Liu S, Zhao S, Jiang Q, Ding B

Abstract
Multidrug resistance (MDR) is a major obstacle in the clinical treatment of cancer. Herein, we report a facile strategy to construct a versatile DNA nanostructure as a co-delivery vector of RNA interference (RNAi) and chemo-drugs to combat multidrug-resistant tumor (MCF-7R) in vitro and in vivo. In our 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 chemo-drug (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.

PMID: 30288887 [PubMed - as supplied by publisher]