title: pH-sensitive nanoparticles of poly(L-histidine)-poly(lactide-co-glycolide)-tocopheryl polyethylene glycol succinate for anti-tumor drug delivery.
abstract: A novel pH-sensitive polymer, poly(L-histidine)-poly(lactide-co-glycolide)-tocopheryl polyethylene glycol succinate (PLH-PLGA-TPGS), was synthesized to design a biocompatible drug delivery system for cancer chemotherapy. The structure of the PLH-PLGA-TPGS copolymer was confirmed by (1)H-NMR, FTIR and GPC. The apparent pKa of the PLH-PLGA-TPGS copolymer was calculated to be 6.33 according to the acid-base titration curve. The doxorubicin (DOX)-loaded nanoparticles (PLH-PLGA-TPGS nanoparticles and PLGA-TPGS nanoparticles) and corresponding blank nanoparticles were prepared by a co-solvent evaporation method. The blank PLH-PLGA-TPGS nanoparticles showed an acidic pH-induced increase in particle size. The DOX-loaded nanoparticles based on PLH-PLGA-TPGS showed a pH-triggered drug-release behavior under acidic conditions. The results of in vitro cytotoxicity experiment on MCF-7 and MCF-7/ADR cells showed that the DOX-loaded PLH-PLGA-TPGS nanoparticles resulted in lower cell viability versus the PLGA-TPGS nanoparticles and free DOX solution. Confocal laser scanning microscopy images showed that DOX-loaded PLH-PLGA-TPGS nanoparticles were internalized by MCF-7/ADR cells after 1 and 4h incubation and most of them accumulated in lysosomes to accelerate DOX release under acidic conditions. In summary, the PLH-PLGA-TPGS nanoparticles have great potential to be used as carriers for anti-tumor drug delivery.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China; School of Pharmacy, Dalian Medical University, Dalian 116044, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Lipeng
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Second Affiliated Hospital of Dalian Medical University, Dalian 116011, People's Republic of China.
authors.forename: Tangna
authors.initials: T
authors.lastname: Hao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Mingxi
authors.initials: M
authors.lastname: Qiao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China; School of Pharmacy, Medical College of Soochow University, Suzhou 215123, People's Republic of China. Electronic address: chendawei@syphu.edu.cn.
authors.forename: Dawei
authors.initials: D
authors.lastname: Chen
authors.affiliation: Shenzhen Key Lab of Gene and Antibody Therapy, Center for Biotech and Bio-Medicine and Division of Life Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, People's Republic of China. Electronic address: mei.lin@sz.tsinghua.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006639:Histidine / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014810:Vitamin E / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D014810:Vitamin E; C033223:polyhistidine; D011098:Polyglactin 910; D006639:Histidine; D004317:Doxorubicin; C014225:tocophersolan
keywords: Copolymer nanoparticles; Cytotoxicity; Doxorubicin; Multi-drug resistance; pH-sensitive