期刊
SCIENCE BULLETIN
卷 64, 期 10, 页码 705-714出版社
ELSEVIER
DOI: 10.1016/j.scib.2019.04.019
关键词
Cancer chemosensitization; Multidrug resistance; P-glycoprotein; pH-responsive; Magnetic resonance imaging
资金
- National Basic Research Development Program of China [2017YFA0205201, 2018YFA0107301]
- National Natural Science Foundation of China [81422023, 81871404, 81603015, U1705281, U1505221]
- Fundamental Research Funds for the Central Universities [20720160065, 20720150141]
- Program for New Century Excellent Talents in University, China [NCET-13-0502]
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. (C) 2019 Science China Press. Published by Elsevier B.V. and Science China Press. All rights reserved.
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