title: N-Boc-histidine-capped PLGA-PEG-PLGA as a smart polymer for drug delivery sensitive to tumor extracellular pH.
abstract: A pH-sensitive polymer was synthesized by introducing the N-Boc-histidine to the ends of a PLGA-PEG-PLGA block copolymer. The synthesized polymer was confirmed to be biodegradable and biocompatible, well dissolved in water and forming micelles above the CMC. DOX was employed as a model anticancer drug. In vitro drug release from micelles of N-Boc-histidine-capped PLGA-PEG-PLGA exhibited significant difference between pH = 6.2 and pH = 7.4, whereas DOX release from micelles composed of un-capped virgin polymers was not significantly sensitive to medium pH. Uptake of DOX from micelles of the new polymer into MDA-MB-435 solid tumor cells was also observed, and pH sensitivity was confirmed. Hence, the N-Boc-histidine capped PLGA-PEG-PLGA might be a promising material for tumor targeting.
authors.affiliation: Key Laboratory of Molecular Engineering of Polymers of Ministry of Education, Department of Macromolecular Science, Laboratory of Advanced Materials, Fudan University, Shanghai, China.
authors.forename: Guangtao
authors.initials: G
authors.lastname: Chang
authors.forename: Chong
authors.initials: C
authors.lastname: Li
authors.forename: Weiyue
authors.initials: W
authors.lastname: Lu
authors.forename: Jiandong
authors.initials: J
authors.lastname: Ding
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000378:metabolism / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry; D045744:Cell Line, Tumor / Q000187:drug effects; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008422:Materials Testing; D008823:Micelles; D015394:Molecular Structure; D009369:Neoplasms / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D011098:Polyglactin 910 / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000903:Antibiotics, Antineoplastic; D001672:Biocompatible Materials; D004337:Drug Carriers; D008823:Micelles; C528571:poly(lactic-co-glycolic acid)-polyethylene glycol-poly(lactic-co-glycolic acid); D011098:Polyglactin 910; D011092:Polyethylene Glycols; D006639:Histidine; D004317:Doxorubicin