文献类型：期刊文献

英文题名：A telomerase-responsive nanoprobe with theranostic properties in tumor cells

作者：Zhang, He-Hua[1];Zhao, Li-Dong[1];Zuo, Peng[1];Yin, Bin-Cheng[1,2,3];Ye, Bang-Ce[1,2,3]

机构：[1]East China Univ Sci & Technol, Lab Biosyst & Microanal, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Zhejiang Univ Technol, Coll Pharmaceut Sci, Collaborat Innovat Ctr Yangtze River Delta Reg Gr, Inst Engn Biol & Hlth, Hangzhou 310014, Peoples R China;[3]Shihezi Univ, Sch Chem & Chem Engn, Shihezi 832000, Xinjiang, Peoples R China

年份：2020

卷号：215

外文期刊名：TALANTA

收录：;EI(收录号：20201108300141);WOS:【SCI-EXPANDED(收录号:WOS:000528209200015)】；

基金：This work was jointly supported by the National Natural Science Foundation of China (Grants 21822402, 21675052, 31730004), the Fundamental Research Funds for the Central Universities, and the Research Program of State Key Laboratory of Bioreactor Engineering.

语种：英文

外文关键词：Nanoprobe; Telomerase; Theranostic; Multidrug resistance; P-glycoprotein

摘要：Multidrug resistance (MDR) is the main cause of treatment failure in clinical cancer chemotherapy due to the presence of P-glycoproteins (P-gp), which widely exist in stubborn drug-resistant tumor membranes and actively pump drugs from inside the tumor cell to the outside. In this study, we report a novel telomerase-responsive nanoprobe with theranostic properties for inhibiting P-gp expression and reversing MDR by gene silencing. This nanoprobe is composed of an AuNP assembled with telomerase primer, antisense oligonucleotide (ASO), and doxorubicin (Dox). When the designed nanoprobe is uptaken by the MDR cancer cells, the Dox and ASO are specifically released due to the extension of telomerase primer triggered by telomerase. The released ASO specifically hybridizes with multidrug resistance 1 (MDR1) mRNA sequence, which encodes the P-gp. As a result, the expression of P-gp is inhibited and the efflux of Dox is prevented with reduced MDR in cancerous cells. The results demonstrate that the nanoprobe based on telomerase switching for drug release and gene silencing, can both target cancer cells for delivering drugs and overcome the effect of efflux pumps. This work presents a novel paradigm for theranostics of MDR cancer and enhances the efficacy of chemotherapeutics.