Effective delivery of an angiogenesis inhibitor by neovessel-targeted liposomes |
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Authors: | Katanasaka Y Ida T Asai T Maeda N Oku N |
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Affiliation: | aDepartment of Medical Biochemistry, School of Pharmaceutical Sciences and Global COE, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan;bNippon Fine Chemical Co. Ltd., Takasago, Hyogo 676-0074, Japan |
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Abstract: | Angiogenesis is critical for tumor growth and metastasis, and several angiogenesis inhibitors have been developed for the treatment of cancer. Previously, we identified angiogenic vessel-homing peptide, Ala-Pro-Arg-Pro-Gly (APRPG), by use of a phage-displayed peptide library. APRPG peptide-modified liposomes have been revealed to be useful for the delivery of encapsulated drugs to angiogenic vasculature in tumor-bearing animals. In the present study, to assess the usefulness of APRPG-PEG-modified liposomes as a carrier of angiogenesis inhibitors in vitro and in vivo, we designed and validated APRPG-PEG-modified liposomal angiogenesis inhibitor. SU1498, an inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinase, was successfully encapsulated into the liposomes. APRPG-PEG-modified liposomal SU1498 inhibited VEGF-stimulated endothelial cell proliferation in vitro. Moreover, APRPG-PEG-modified liposomal SU1498 significantly decreased tumor microvessel density in Colon26 NL-17 cell-bearing mice and prolonged the survival time of the mice. These findings suggest that APRPG-PEG-modified liposomes effectively deliver SU1498 to angiogenic endothelial cells in tumors and thus inhibit tumor-induced angiogenesis. |
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Keywords: | Angiogenesis Drug delivery systems Angiogenesis inhibitor APRPG-modified liposomes SU1498 |
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