title: Self-assemblies of pH-activatable PEGylated multiarm poly(lactic acid-co-glycolic acid)-doxorubicin prodrugs with improved long-term antitumor efficacies.
abstract: Two pH-activatable star-shaped prodrugs are synthesized through the condensation reaction between Y- or dumbbell-shaped poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PEG-PLGA) copolymer and acid-sensitive cis-aconityl-doxorubicin. The prodrugs self-assemble into micelles with favorable hydrodynamic radii and relatively low critical micelle concentrations. In vitro DOX release from prodrug micelles is accelerated by the decrease of the PLGA content or at the late endosomal pH. The efficient cellular uptake and intracellular DOX release of the prodrug micelles are confirmed and the improved long-term anti-proliferative activities of prodrug micelles are revealed. These features suggest that the prodrugs provide a favorable approach to construct effective polymeric drug delivery systems for malignancy therapy.
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Ding
authors.forename: Di
authors.initials: D
authors.lastname: Li
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhuang
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016503:Drug Delivery Systems; D011992:Endosomes / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008823:Micelles; D011100:Polyglycolic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D008823:Micelles; D011355:Prodrugs; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin
keywords: amphiphiles; malignancy therapy; pH-activatable; prodrug; self-assembly