title: Preparation and antitumor activity of a polymeric derivative of methotrexate.
abstract: A polymer-drug conjugate was developed by conjugating amino bonds of methotrexate (MTX) to succinoylated α,β-poly[(2-hydroxyethyl)-L-aspartamide] (PHEA). The therapeutic efficacy of PHEA-MTX was evaluated in vitro and in vivo. PHEA-MTX showed sustained release properties when incubated in pH 5.5 and pH 7.4 buffering solutions at 37°C. PHEA-MTX induced MG63 cell apoptosis in a time-dependent and concentration-dependent manner in vitro and inhibited the growth of S180 sarcoma in vivo. PHEA-MTX was more potent and, more importantly, displayed less systemic toxicity than free MTX. The enhanced therapeutic effects of PHEA-MTX suggest that the PHEA-MTX conjugate may have a greater potential for chemotherapy of cancers.
authors.affiliation: Department of Orthopedics, Jinling Hospital, Nanjing, China.
authors.forename: Guangxin
authors.initials: G
authors.lastname: Zhou
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Cheng
authors.forename: Sujia
authors.initials: S
authors.lastname: Wu
authors.forename: Xiqun
authors.initials: X
authors.lastname: Jiang
authors.forename: Xin
authors.initials: X
authors.lastname: Shi
authors.forename: Jiangning
authors.initials: J
authors.lastname: Chen
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D006801:Humans; D008727:Methotrexate / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D012516:Osteosarcoma / Q000188:drug therapy*; D010455:Peptides; D011108:Polymers
chemical_list: D000964:Antimetabolites, Antineoplastic; C579676:PHEA-MTX conjugate; D010455:Peptides; D011108:Polymers; D008727:Methotrexate