title: Acid-Cleavable Unimolecular Micelles from Amphiphilic Star Copolymers for Triggered Release of Anticancer Drugs.
abstract: In this contribution, amphiphilic star copolymers (H40-star-PCL-a-PEG) with an H40 hyperbranched polyester core and poly(ε-caprolactone)-a-poly(ethylene glycol) copolymer arms linked with acetal groups are synthesized using ring-opening polymerization and a copper (I)-catalyzed alkyne-azide cycloaddition click reaction. The acid-cleavable acetal groups between the hydrophilic and hydrophobic segments of the arms endow the amphiphilic star copolymers with pH responsiveness. In aqueous solution, unimolecular micelles can be formed with good stability and a unique acid degradability, as is desirable for anticancer drug carriers. For the model drug of doxorubicin, the in vitro release behavior, intracellular release, and inhibition of proliferation of HeLa cells show that the acid-cleavable unimolecular micelles with anticancer activity can be dissociated in an acidic environment and efficiently internalized by HeLa cells. Due to the acid-cleavable and biodegradable nature, unimolecular micelles from amphiphilic star copolymers are promising for applications in intracellular drug delivery for cancer chemotherapy.
authors.affiliation: Shaanxi Key Laboratory of Macromolecular Science and Technology, School of Science, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, P. R. China.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Shaanxi Key Laboratory of Macromolecular Science and Technology, School of Science, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
authors.forename: Heng
authors.initials: H
authors.lastname: Chen
authors.affiliation: Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, P. R. China.
authors.forename: Zhangfa
authors.initials: Z
authors.lastname: Song
authors.affiliation: PLA No. 323 Hospital, Xi'an, Shaanxi Province, 710054, P. R. China.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Shaanxi Key Laboratory of Macromolecular Science and Technology, School of Science, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
authors.forename: Xingyi
authors.initials: X
authors.lastname: Dai
authors.affiliation: Shaanxi Key Laboratory of Macromolecular Science and Technology, School of Science, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Kong
mesh_terms: D004317:Doxorubicin / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D011091:Polyesters / Q000008:administration & dosage / Q000138:chemical synthesis; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000138:chemical synthesis; D011108:Polymers / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011108:Polymers; C016240:polycaprolactone; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: acetal groups; pH responsiveness; star copolymers; triggered release; unimolecular micelles