論文

査読有り
2007年9月

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

MOLECULAR PHARMACEUTICS
  • 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

4
5
開始ページ
713
終了ページ
722
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1021/mp060132k
出版者・発行元
AMER CHEMICAL SOC

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.

Web of Science ® 被引用回数 : 236

リンク情報
DOI
https://doi.org/10.1021/mp060132k
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000249926400010&DestApp=WOS_CPL
ID情報
  • DOI : 10.1021/mp060132k
  • ISSN : 1543-8384
  • Web of Science ID : WOS:000249926400010

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