Environmentally responsive dual-targeting nanotheranostics for overcoming cancer multidrug resistance  

作　　者：Caixia Yang Xin Pang Weihai Chen Xiaoyong Wang Gan Lin Chengchao Chu Xianzheng Zhang Xianming Deng Xiaoyuan Chen Gang Liu 

机构地区：[1]State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China [2]Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, China [3]State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, China [4]Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD 20892, USA

出　　处：《Science Bulletin》2019年第10期705-714,共10页科学通报（英文版）

基　　金：supported by the National Basic Research Development Program of China(2017YFA0205201 and 2018YFA0107301);the National Natural Science Foundation of China(81422023,81871404,81603015,U1705281,and U1505221);the Fundamental Research Funds for the Central Universities(20720160065,and 20720150141);the Program for New Century Excellent Talents in University,China(NCET-13-0502)

摘　　要：The development of multiple drug resistance(MDR) to chemotherapy and subsequent treatment failures are major obstacles in cancer therapy. An attractive option for combating MDR is inhibiting the expression of P-glycoprotein(P-gp) in tumor cells. Here, we report a novel chemosensitizing agent, XMD8-92,which can down-regulate P-gp. To enhance the specificity of MDR chemotherapy, a promising nanotheranostic micelle system based on poly(ethylene glycol)-blocked-poly(L-leucine)(PEG-b-Leu) was developed to simultaneously carry the anticancer drug doxorubicin, chemosensitizing agent XMD8-92, and superparamagnetic iron oxide nanoparticles(SPIOs). Featured with MDR environmentally responsive dual-targeting capability, controllable drug delivery, and efficient magnetic resonance(MR) imaging characteristics, the prepared nanotheranostics(DXS@NPs) showed outstanding in vitro cytotoxicity on MDR cells(SCG 7901/VCR) with only 53% of cells surviving compared to 90% of DOX-treated cells.Furthermore, efficient tumor inhibition and highly reduced systemic toxicity were exhibited by MDR tumor-bearing mice treated with DXS@NPs. Overall, the environmentally responsive dual-targeting nanotheranostics represent a promising approach for overcoming cancer MDR.The development of multiple drug resistance(MDR) to chemotherapy and subsequent treatment failures are major obstacles in cancer therapy. An attractive option for combating MDR is inhibiting the expression of P-glycoprotein(P-gp) in tumor cells. Here, we report a novel chemosensitizing agent, XMD8-92,which can down-regulate P-gp. To enhance the specificity of MDR chemotherapy, a promising nanotheranostic micelle system based on poly(ethylene glycol)-blocked-poly(L-leucine)(PEG-b-Leu) was developed to simultaneously carry the anticancer drug doxorubicin, chemosensitizing agent XMD8-92, and superparamagnetic iron oxide nanoparticles(SPIOs). Featured with MDR environmentally responsive dual-targeting capability, controllable drug delivery, and efficient magnetic resonance(MR) imaging characteristics, the prepared nanotheranostics(DXS@NPs) showed outstanding in vitro cytotoxicity on MDR cells(SCG 7901/VCR) with only 53% of cells surviving compared to 90% of DOX-treated cells.Furthermore, efficient tumor inhibition and highly reduced systemic toxicity were exhibited by MDR tumor-bearing mice treated with DXS@NPs. Overall, the environmentally responsive dual-targeting nanotheranostics represent a promising approach for overcoming cancer MDR.

关 键 词：CANCER CHEMOSENSITIZATION MULTIDRUG resistance P-GLYCOPROTEIN PH-RESPONSIVE Magnetic resonance imaging 

分 类 号：N[自然科学总论]