title: pH and redox dual-responsive biodegradable polymeric micelles with high drug loading for effective anticancer drug delivery.
abstract: Diblock copolymers of poly(ethylene glycol) (PEG) and biodegradable polycarbonate functionalized with GSH-sensitive disulfide bonds and pH-responsive carboxylic acid groups were synthesized via organocatalytic ring-opening polymerization of functional cyclic carbonates with PEG having different molecular weights as macroinitiators. These narrowly-dispersed polymers had predictable molecular weights, and were used to load doxorubicin (DOX) into micelles primarily through ionic interactions. The DOX-loaded micelles exhibited the requisite small particle size (<100 nm), narrow size distribution and high drug loading capacity. When exposed to endolysosomal pH of 5.0, drug release was accelerated by at least two-fold. The introduction of GSH further expedited DOX release. Effective DOX release enhanced cytotoxicity against cancer cells. More importantly, the DOX-loaded micelles with the optimized composition showed excellent antitumor efficacy in nude mice bearing BT-474 xenografts without inducing toxicity. These pH and redox dual-responsive micelles have the potential as delivery carriers to maximize the therapeutic effect of anticancer drugs.
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore.
authors.forename: Jye Yng
authors.initials: JY
authors.lastname: Teo
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore.
authors.forename: Willy
authors.initials: W
authors.lastname: Chin
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore.
authors.forename: Xiyu
authors.initials: X
authors.lastname: Ke
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore.
authors.forename: Shujun
authors.initials: S
authors.lastname: Gao
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore.
authors.forename: Shaoqiong
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore.
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
authors.affiliation: IBM Almaden Research Center, San Jose, CA 95120, USA. Electronic address: hedrick@us.ibm.com.
authors.forename: James L
authors.initials: JL
authors.lastname: Hedrick
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore 138669, Singapore. Electronic address: yyyang@ibn.a-star.edu.sg.
authors.forename: Yi Yan
authors.initials: YY
authors.lastname: Yang
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D002470:Cell Survival; D004317:Doxorubicin; D004337:Drug Carriers; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D010084:Oxidation-Reduction; D011092:Polyethylene Glycols; D011108:Polymers
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Anticancer drug delivery; GSH-sensitive; In vivo anticancer efficacy; Polycarbonate micelles; pH-sensitive