title: Micelles of enzymatically synthesized PEG-poly(amine-co-ester) block copolymers as pH-responsive nanocarriers for docetaxel delivery.
abstract: A series of PEGylated poly(amine-co-ester) terpolymers were successfully synthesized in one step via lipase-catalyzed copolymerization of ω-pentadecalactone (PDL), diethyl sebacate (DES), and N-methyldiethanolamine (MDEA) comonomers in the presence of poly(ethylene glycol) methyl ether as a chain-terminating agent. The resultant amphiphilic poly(ethylene glycol)-poly(PDL-co-MDEA-co-sebacate) (PEG-PPMS) block copolymers consisted of hydrophilic PEG chain segments and hydrophobic random PPMS chain segments, which self-assembled in aqueous medium to form stable, nanosized micelles at physiological pH of 7.4. Upon decreasing the medium pH from 7.4 to 5.0, the copolymer micelles swell significantly due to protonation of the amino groups in the micelle PPMS cores. Correspondingly, docetaxel (DTX)-encapsulated PEG2K-PPMS copolymer micelles showed gradual sustained drug release at pH of 7.4, but remarkably accelerated DTX release at acidic pH of 5.0. The drug-loaded micelle particles were readily internalized by SK-BR-3 cancer cells and, compared to free DTX drug, DTX-loaded micelles of the copolymers with optimal compositions exhibited enhanced potency against the cells. Biodegradable PEG-PPMS copolymer micelles represent a new type of promising, pH-responsive nanocarriers for anticancer drug delivery, and the drug release rate from the micelles can be systematically controlled by both pH and the copolymer composition.
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Ling Nan Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
authors.forename: Xingen
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Guangzhou, Guangdong 510060, China.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
authors.forename: Di
authors.initials: D
authors.lastname: Gao
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, China. Electronic address: bmeliu@gmail.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Molecular Innovations Center, Yale University, 600 West Campus Drive, West Haven, CT 06516, United States. Electronic address: zhaozhong.jiang@yale.edu.
authors.forename: Zhaozhong
authors.initials: Z
authors.lastname: Jiang
mesh_terms: D002175:Candida / Q000201:enzymology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D004983:Ethanolamines / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008049:Lipase / Q000378:metabolism*; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D055672:Static Electricity; D043823:Taxoids / Q000494:pharmacology*
chemical_list: D004337:Drug Carriers; D004983:Ethanolamines; D018942:Macrolides; D008823:Micelles; D011091:Polyesters; D043823:Taxoids; C571591:omega-pentadecalactone; C546772:polyethylene sebacate; D000077143:Docetaxel; C008430:N-methyldiethanolamine; D011092:Polyethylene Glycols; D008049:Lipase
keywords: Docetaxel delivery; Lipase; Micelle; Poly(amine-co-ester); pH-responsive