Targeted drug delivery to tumor vasculature by a carbohydrate mimetic peptide

Shingo Hatakeyama, Kazuhiro Sugihara, Toshiaki K. Shibata, Jun Nakayama, Tomoya O. Akama, Naoaki Tamura, Shuk Man Wong, Andrey A. Bobkov, Yutaka Takano, Chikara Ohyama, Minoru Fukuda, Michiko N. Fukuda

研究成果: Article査読

65 被引用数 (Scopus)

抄録

Although numerous carbohydrates play significant roles in mammalian cells, carbohydrate-based drug discovery has not been explored due to the technical difficulty of chemically synthesizing complex carbohydrate structures. Previously, we identified a series of carbohydrate mimetic peptides and found that a 7-mer peptide, designated I-peptide, inhibits hematogenous carbohydrate-dependent cancer cell colonization. During analysis of the endothelial surface receptor for I-peptide, we found that I-peptide bound to annexin 1 (Anxa1). Because Anxa1 is a highly specific tumor vasculature surface marker, we hypothesized that an I-peptide-like peptide could target anticancer drugs to the tumor vasculature. This study identifies IFLLWQR peptide, designated IF7, as homing to tumors. When synthetic IF7 peptide was conjugated to fluorescent Alexa 488 (A488) and injected intravenously into tumor-bearing mice, IF7-A488 targeted tumors within minutes. IF7 conjugated to the potent anticancer drug SN-38 and injected intravenously into nude mice carrying human colon HCT116 tumors efficiently suppressed tumor growth at lowdosages with no apparent side effects. These results suggest that IF7 serves as an efficient drug delivery vehicle by targeting Anxa1 expressed on the surface of tumor vasculature. Given its extremely specific tumor-targeting activity, IF7 may represent a clinically relevant vehicle for anticancer drugs.

本文言語English
ページ(範囲)19587-19592
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
108
49
DOI
出版ステータスPublished - 06-12-2011
外部発表はい

All Science Journal Classification (ASJC) codes

  • 一般

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