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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.


Guangxin Zhou, Xiaoyun Cheng, Sujia Wu, Xiqun Jiang, Xin Shi, Jiangning Chen, Junfeng Zhang, Jianning Zhao. Preparation and antitumor activity of a polymeric derivative of methotrexate. The American journal of the medical sciences. 2012 Oct;344(4):294-9

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PMID: 22885620

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