期刊
CARBOHYDRATE POLYMERS
卷 198, 期 -, 页码 142-154出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2018.06.079
关键词
Dextran; Ortho ester; Nanogel; P-glycoprotein; Multidrug resistance
资金
- National Natural Science Foundation of China [51503001]
- Research Foundation for Key Program of Education Department of Anhui Province of China [KJ2016A030]
- Doctor Research Foundation of Anhui University [J10113190075]
- Academic and Technology Introduction Project of Anhui University [AU02303203]
Herein pH-sensitive nanogels (NG1) and P-glycoprotein-repressive nanogels (NG2) were prepared by copolymerization between an ortho ester crosslinker (OEAM) and tocopheryl polyethylene glycol succinate (TPGS)-free or conjugated dextran. Nanogels with or without TPGS possessed a uniform diameter (similar to 180nm) and excellent stability in various physiological environments. Doxorubicin (DOX) was successfully loaded into NG1 and NG2 to give NG1/DOX and NG2/DOX, both of them showed appropriate drug release profiles under mildly acidic conditions (pH 5.0). NG2/DOX possessed higher drug enrichment and lethality than NG1/DOX did on MCF-7/ADR cells. Analysis of corresponding index of efflux activity showed that NG2 could induce depolarization of mitochondrial membrane and interfere with ATP metabolism. NG2/DOX also displayed increased penetration and growth inhibition on MCF-7/ADR multicellular spheroids. These results demonstrated that pH-sensitive TPGS-functionalized nanogels (NG2) as drug carriers had great potential to suppress drug efflux in MCF-7/ADR cells and even overcome MDR on cancer cells.
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