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A Tailored DNA Nanoplatform for Synergistic RNAi‐/Chemotherapy of Multidrug‐Resistant Tumors
Author(s) -
Liu Jianbing,
Song Linlin,
Liu Shaoli,
Zhao Shuai,
Jiang Qiao,
Ding Baoquan
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201809452
Subject(s) - nanocarriers , rna interference , small hairpin rna , multiple drug resistance , doxorubicin , cancer research , survivin , p glycoprotein , genetic enhancement , drug resistance , dna , chemistry , biology , rna , gene , pharmacology , chemotherapy , drug , biochemistry , genetics
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.