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

J Control Release. 2004 Oct 19;99(3):369-81. doi: 10.1016/j.jconrel.2004.07.024.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Cisplatin / pharmacology
  • Combined Modality Therapy / methods*
  • Disease Models, Animal
  • Drug Delivery Systems / methods*
  • Drug Screening Assays, Antitumor / methods
  • Female
  • Fluorescein-5-isothiocyanate / analogs & derivatives*
  • Fluorescein-5-isothiocyanate / metabolism
  • Fluorescein-5-isothiocyanate / pharmacology
  • Indium Radioisotopes
  • Liposomes / chemistry
  • Liposomes / metabolism
  • Liposomes / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / radiotherapy*
  • Neoplasms, Experimental / blood supply
  • Neoplasms, Experimental / radiotherapy*
  • Neoplasms, Experimental / ultrastructure
  • Neutron Capture Therapy*
  • Radiation-Sensitizing Agents / pharmacology
  • Radiometry / adverse effects
  • Radiometry / methods
  • Skin / blood supply
  • Skin / drug effects
  • Skin / ultrastructure
  • Tumor Cells, Cultured
  • Wheat Germ Agglutinins / metabolism
  • Wheat Germ Agglutinins / pharmacology

Substances

  • Angiogenesis Inhibitors
  • Indium Radioisotopes
  • Liposomes
  • Radiation-Sensitizing Agents
  • Wheat Germ Agglutinins
  • fluorescein isothiocyanate-wheat germ agglutinin
  • Fluorescein-5-isothiocyanate
  • Cisplatin