Preclinical study of the cyclodextrin-polymer conjugate of camptothecin CRLX101 for the treatment of gastric cancer

Shikha Gaur, Linling Chen, Terence Yen, Yafan Wang, Bingsen Zhou, Mark Davis, Yun Yen

研究成果: 雜誌貢獻文章同行評審

44 引文 斯高帕斯(Scopus)

摘要

Camptothecin showed remarkable anticancer activity in animal models of cancer but was restricted in clinical use for its adverse toxicity in patients. The preclinical efficacy of CRLX101, a nanoparticle (NP) assembly containing cyclodextrin-based polymer and camptothecin was evaluated by in vitro cytotoxicity in gastric cancer cell lines and in vivo antitumor effects in human gastric cancer cell line BGC823 xenografts. Treated tumor sections were analyzed for presence of NPs and compared with vehicle control tumors for hypoxia and angiogenesis. Gastric cancer cell lines showed high in vitro cytotoxicity for CRLX101 and also showed strong antitumor activity in vivo. Electron micrographs revealed the intracellular presence of NPs in close proximity to vesicles. A significant decrease in expressions of carbonic anhydrase, VEGF, and CD31 proteins in treated tumors indicated an inhibition of hypoxia and angiogenesis. The results provide preclinical data for gastric adenocarcinoma. From the Clinical Editor: This study describes a nanoparticle assembly containing cyclodextrin-based polymer and camptothecin, resulting in increased bioavailability of camptothecin, an effective but toxic anti-cancer agent. The antitumor effects and safety profile were demonstrated in a gastric carcinoma cell line.

原文英語
頁(從 - 到)721-730
頁數10
期刊Nanomedicine: Nanotechnology, Biology, and Medicine
8
發行號5
DOIs
出版狀態已發佈 - 七月 1 2012
對外發佈

ASJC Scopus subject areas

  • 醫藥(雜項)
  • 生物工程
  • 生物醫學工程
  • 分子醫學
  • 材料科學(全部)
  • 藥學科學

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