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Advanced Chemoembolization by Anti-angiogenic Calcium-Phosphate Ceramic Microspheres Targeting the Vascular Heterogeneity of Cancer Xenografts.

The purpose of the present study was to develop an advanced method of anti-angiogenic chemoembolization to target morphological vascular heterogeneity in tumors and further the therapeutic efficacy of cancer treatment. This new chemoembolization approach was designed using resorbable calcium-phosphate ceramic microspheres (CPMs), in a mixture of three different sizes, which were loaded with an anti-angiogenic agent to target the tumor vasculature in highly angiogenic solid tumors in humans in vivo. The human uterine carcinosarcoma cell line, FU-MMT-3, was used in this study because the tumor is highly aggressive and exhibits a poor response to radiotherapy and chemotherapeutic agents that are in current use. CPMs loaded with TNP-470, an anti-angiogenic agent, were injected into FU-MMT-3 xenografts in nude mice three times per week for 8 weeks. The treatment with TNP-470-loaded CPMs of three different diameters achieved a greater suppression of tumor growth in comparison to treatment with single-size TNP-470-loaded CPMs alone, and the control. Severe loss of body weight was not observed in any mice treated with any size of TNP-470-loaded CPMs. These results suggest that treatment with a mixture of differently-sized anti-angiogenic CPMs might be more effective than treatment with CPMs of a single size. This advanced chemoembolization method, which incorporated an anti-angiogenic agent to target the morphological vascular heterogeneity of tumors may contribute to effective treatment of locally advanced or recurrent solid tumors.