Radiation-guided drug delivery to tumor blood vessels results in improved tumor growth delay

Ling Geng, Katherine Osusky, Sekhar Konjeti, Allie Fu, Dennis Hallahan

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Tumor blood vessels are biological targets for cancer therapy. In this study, a tumor vasculature targeting system that consisted of liposomes and lectin (WGA) was built. Liposomes were used to carry a number of liposome-friendly anti-tumoral agents along with WGA, a lectin which posseses a specific affinity for binding to inflamed endothelial cells. In order to target tumor vasculature, inflammation of endothelial cells was induced by radiation. Because ionizing radiation induces an inflammatory response in tumor vasculature, lectin-conjugates were utilized to determine whether radiation can be used to target drug delivery to tumor vessels. Wheat germ agglutinin (WGA) is one such lectin that binds to inflamed microvasculature. WGA was conjugated to liposomes containing cisplatin and administered to tumor bearing mice. Tumor growth delay was used to analyze the efficacy of cytotoxicity. FITC-conjugated WGA accumulated within irradiated tumor microvasculature. WGA was conjugated to liposomes and labeled with 111In. This demonstrated radiation-inducible tumor-selective binding. WGA-liposome-conjugates were loaded with Cisplatin and administered to mice bearing irradiated tumors. Tumors treated with a combination of liposome encapsulated cisplatin together with radiation showed a significant increase in tumor growth delay as compared to radiation alone. These findings demonstrate that ionizing radiation can be used to guide drug delivery to tumor microvasculature.

Original languageEnglish
Pages (from-to)369-381
Number of pages13
JournalJournal of Controlled Release
Volume99
Issue number3
DOIs
StatePublished - Oct 19 2004

Keywords

  • Radiation-guided drug delivery
  • Tumor blood vessel
  • Tumor growth delay

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