title: Terminal modification of polymeric micelles with π-conjugated moieties for efficient anticancer drug delivery.
abstract: High drug loading content is the critical factor to polymeric micelles for efficient chemotherapy. Small molecules of cinnamic acid, 7-carboxymethoxy coumarin and chrysin with different π-conjugated moieties were immobilized on the terminal hydroxyl groups of PCL segments in mPEG-PCL micelles to improve drug loading content via the evocation of π-π stacking interaction between doxorubicin (DOX) and polymeric micelles. The modification of π-conjugated moieties enhanced the capability of crystallization of mPEG-PCL block copolymers. The drug loading content increased dramatically from 12.9% to 25.5% after modification. All the three modified mPEG-PCL micelles were nontoxic to cells. Chrysin modified polymeric micelles exhibited the most efficient anticancer activity. The in vivo anticancer activity of 10 mg/kg DOX dose of chrysin modified micelle formulation for twice injections was comparable to that of 5 mg/kg dose of free DOX·HCl for four injections under the circumstance of same total DOX amount. The systemic toxicity of DOX loaded chrysin modified micelles was significantly reduced. This research provided a facile strategy to achieve polymeric micelles with high drug loading content and efficient anticancer activity both in vitro and in vivo.
authors: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
authors: Yan
authors: Y
authors: Liang
authors: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
authors: Xin
authors: X
authors: Deng
authors: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
authors: Longgui
authors: L
authors: Zhang
authors: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
authors: Xinyu
authors: X
authors: Peng
authors: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
authors: Wenxia
authors: W
authors: Gao
authors: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China. Electronic address: caojun@scu.edu.cn.
authors: Jun
authors: J
authors: Cao
authors: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
authors: Zhongwei
authors: Z
authors: Gu
authors: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China. Electronic address: bhe@scu.edu.cn.
authors: Bin
authors: B
authors: He
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D011108:Polymers / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D014961:X-Ray Diffraction
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers
keywords: Chrysin; Conjugated moieties; Drug delivery; Polymeric micelle; π-π stacking interaction