title: Biodegradable mixed MPEG-SS-2SA/TPGS micelles for triggered intracellular release of paclitaxel and reversing multidrug resistance.
abstract: In this study, a type of multifunctional mixed micelles were prepared by a novel biodegradable amphiphilic polymer (MPEG-SS-2SA) and a multidrug resistance (MDR) reversal agent (d-α-tocopheryl polyethylene glycol succinate, TPGS). The mixed micelles could achieve rapid intracellular drug release and reversal of MDR. First, the amphiphilic polymer, MPEG-SS-2SA, was synthesized through disulfide bonds between poly (ethylene glycol) monomethyl ether (MPEG) and stearic acid (SA). The structure of the obtained polymer was similar to poly (ethylene glycol)-phosphatidylethanolamine (PEG-PE). Then the mixed micelles, MPEG-SS-2SA/TPGS, were prepared by MPEG-SS-2SA and TPGS through the thin film hydration method and loaded paclitaxel (PTX) as the model drug. The in vitro release study revealed that the mixed micelles could rapidly release PTX within 24 h under a reductive environment because of the breaking of disulfide bonds. In cell experiments, the mixed micelles significantly inhibited the activity of mitochondrial respiratory complex II, also reduced the mitochondrial membrane potential, and the content of adenosine triphosphate, thus effectively inhibiting the efflux of PTX from cells. Moreover, in the confocal laser scanning microscopy, cellular uptake and 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assays, the MPEG-SS-2SA/TPGS micelles achieved faster release and more uptake of PTX in Michigan Cancer Foundation-7/PTX cells and showed better antitumor effects as compared with the insensitive control. In conclusion, the biodegradable mixed micelles, MPEG-SS-2SA/TPGS, could be potential vehicles for delivering hydrophobic chemotherapeutic drugs in MDR cancer therapy.
authors: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University.
authors: Kai
authors: K
authors: Dong
authors: School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
authors: Yan
authors: Y
authors: Yan
authors: School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
authors: Pengchong
authors: P
authors: Wang
authors: School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
authors: Xianpeng
authors: X
authors: Shi
authors: School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
authors: Lu
authors: L
authors: Zhang
authors: School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
authors: Ke
authors: K
authors: Wang
authors: School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
authors: Jianfeng
authors: J
authors: Xing
authors: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University.
authors: Yalin
authors: Y
authors: Dong
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D065546:Drug Liberation; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008823:Micelles; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology*; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D014810:Vitamin E / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D010714:Phosphatidylethanolamines; D011108:Polymers; C067972:dioleoyl-N-(monomethoxypolyethylene glycol succinyl)phosphatidylethanolamine; D014810:Vitamin E; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; C014225:tocophersolan; D017239:Paclitaxel
keywords: MCF-7/PTX cells; disulfide bond; mixed micelles; reduction-sensitive; reversal of multidrug resistance