Radiation-guided drug delivery to tumor blood vessels results in improved tumor growth delay
| Autor: | Dennis E. Hallahan, K. Osusky, Ling Geng, Allie Fu, Sekhar R. Konjeti |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Radiation-Sensitizing Agents
Wheat Germ Agglutinins Pharmaceutical Science Inflammation Angiogenesis Inhibitors Mice Drug Delivery Systems Neoplasms medicine Tumor Cells Cultured Animals Cytotoxicity Radiometry Skin Cisplatin Liposome biology business.industry Indium Radioisotopes Lectin Neoplasms Experimental Neutron Capture Therapy Combined Modality Therapy Wheat germ agglutinin Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Immunology Drug delivery Liposomes Cancer research biology.protein Female medicine.symptom Drug Screening Assays Antitumor business Fluorescein-5-isothiocyanate Blood vessel medicine.drug |
| Zdroj: | Journal of controlled release : official journal of the Controlled Release Society. 99(3) |
| ISSN: | 0168-3659 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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