Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published July 2012 | public
Journal Article

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

Abstract

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.

Additional Information

© 2012 Elsevier Inc. Received 8 March 2011. Accepted 22 September 2011. Available online 25 October 2011. The funding for the study was provided by the City of Hope internal funds to Dr. Yun Yen. We thank Dr. David Ann for helpful suggestions; Dr. Li Zhuo, Ms. Sofia Loera, and Ms. Mariko Lee for their help with electron microscopy, histopathological staining, and light microscope imaging, respectively; and Mr. Vincent Ann for editing the manuscript.

Additional details

Created:
August 22, 2023
Modified:
October 18, 2023