title: Enhanced antitumor efficacy by cyclic RGDyK-conjugated and paclitaxel-loaded pH-responsive polymeric micelles.
abstract: Cyclic RGDyK (cRGDyK)-conjugated pH-sensitive polymeric micelles were fabricated for targeted delivery of paclitaxel to prostate cancer cells based on pH-sensitive copolymer poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) (PEOz-PLA) and cRGDyK-PEOz-PLA to enhance antitumor efficacy. The prepared micelles with an average diameter of about 28nm exhibited rapid release behavior at endo/lysosome pH, effectively enhanced the cytotoxicity of paclitaxel to PC-3 cells by increasing the cellular uptake, which was correlated with integrin αvβ3 expression in tumor cells. The active targeting activity of the micelles was further confirmed by in vivo real time near-infrared fluorescence imaging in PC-3 tumor-bearing nude mice. Moreover, the active targeting and pH-sensitivity endowed cRGDyK-conjugated micelles with a higher antitumor effect in PC-3 xenograft-bearing nude mice compared with unmodified micelles and Taxol with negligible systemic toxicity. Therefore, these results suggested that cRGDyK-conjugated pH-sensitive polymeric micelles may be a promising delivery system for efficient delivery of anticancer drugs to treat integrin αvβ3-rich prostate cancers.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Yushu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Jinwen
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: ll@bjmu.edu.cn.
authors.forename: Xinru
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: yanliu@bjmu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000138:chemical synthesis; D004058:Diffusion; D004357:Drug Synergism; D006863:Hydrogen-Ion Concentration; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008823:Micelles; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry / Q000493:pharmacokinetics*; D011108:Polymers / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D039302:Integrin alphaVbeta3; D008823:Micelles; D053769:Nanocapsules; D010456:Peptides, Cyclic; D011108:Polymers; C507169:cyclic arginine-glycine-aspartic acid peptide; D017239:Paclitaxel
keywords: Integrin α(v)β(3); Paclitaxel; Poly(2-ethyl-2-oxazoline)-poly(d,l-lactide); Tumor-targeting; pH-responsive polymeric micelles