Methotrexate conjugated to gold nanoparticles inhibits tumor growth in a syngeneic lung tumor model

Yu-Hung Chen, Chiau Yuang Tsai, Pon Yu Huang, Meng Ya Chang, Pai Chiao Cheng, Chen-Hsi Chou, Dong-Hwang Chen, Chrong-Reen Wang, Ai-Li Shiau, Chao-Liang Wu

研究成果: Article

224 引文 斯高帕斯(Scopus)

摘要

Methotrexate (MTX), a stoichiometric inhibitor of dihydrofolate reductase, is a chemotherapeutic agent for treating a variety of neoplasms. Impairment of drug import into cells and increase in drug export from cells may render cells resistant to MTX. MTX, when locally administered in a soluble form, is rapidly absorbed through capillaries into the circulatory system, which may also account for therapeutic failure in patients. To retain MTX within tumor cells for longer duration and alter its pharmacokinetic behavior, we proposed a new formulation of MTX bound to the gold nanoparticle (AuNP) that serves as drug carriers. In this study, we developed the MTX-AuNP conjugate and examined its cytotoxic effect in vitro and antitumor effect in vivo. Spectroscopic examinations revealed that MTX can be directly bound onto AuNP via the carboxyl group (-COOH) to form the MTX-AuNP complex and kinetically released from the nanoparticles. The accumulation of MTX is faster and higher in tumor cells treated with MTX-AuNP than that treated with free MTX. Notably, MTX-AuNP shows higher cytotoxic effects on several tumor cell lines compared with an equal dose of free MTX. This can be attributed to the "concentrated effect" of MTX-AuNP. Administration of MTX-AuNP suppresses tumor growth in a mouse ascites model of Lewis lung carcinoma (LL2), whereas an equal dose of free MTX had no antitumor effect. In conclusion, these results suggest that by combining nanomaterials with anticancer drugs MTX-AuNP may be more effective than free MTX for cancer treatment.

原文English
頁(從 - 到)713-722
頁數10
期刊Molecular Pharmaceutics
4
發行號5
DOIs
出版狀態Published - 2007 九月 1

    指紋

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmaceutical Science

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