title: Preparation of multilocation reduction-sensitive core crosslinked folate-PEG-coated micelles for rapid release of doxorubicin and tariquidar to overcome drug resistance.
abstract: Herein, we prepared folate-targeting core crosslinked polymeric micelles (CCL/FA) containing multiple disulfide bonds located at the interface and core of the micelles to co-deliver doxorubicin (DOX) and the P-glycoprotein (P-gp) inhibitor tariquidar (TQR) for reversing drug resistance. The stability and redox-responsive behavior of the CCL/FA micelles was evaluated through the changes in morphology, molecular weight and hydrodynamic size. On the one hand, the micelles possessed good stability, which led to the suppression of drug release from the CCL micelles in the physiological environment. On the other hand, under reductive conditions, the CCL micelles collapsed rapidly and accelerated drug release markedly. In vitro cytotoxicity measurements, combined with confocal laser scanning microscopy (CLSM) and flow cytometry, confirmed that the dual-drug-loaded micelles exhibited obviously higher cytotoxicity to MCF-7/ADR-resistant cells than free DOX · HCl, single-drug loaded CCL micelles and nontargeted CCL micelles. The results imply that co-delivering DOX and TQR by CCL/FA micelles may be a promising way of overcoming multidrug resistance in tumor treatments.
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Science, Wuhan University, Wuhan, 430072, People's Republic of China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Yi
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Xu
authors.forename: Gongdao
authors.initials: G
authors.lastname: Yuan
authors.forename: Renxi
authors.initials: R
authors.lastname: Zhuo
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers; D004339:Drug Compounding / Q000379:methods; D065546:Drug Liberation; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D058973:Folate Receptors, GPI-Anchored / Q000235:genetics / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D061986:MCF-7 Cells; D008823:Micelles; D058990:Molecular Targeted Therapy; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D058973:Folate Receptors, GPI-Anchored; D008823:Micelles; D011108:Polymers; D011725:Pyridines; D011804:Quinolines; D011092:Polyethylene Glycols; D004317:Doxorubicin; D005492:Folic Acid; C402343:tariquidar