LHRH Targeted Chonderosomes of Mitomycin C In Breast Cancer: An In Vitro / In Vivo Study

Abstract

BACKGROUND: Mitomycin C (MMC) is an anti-cancer drug used for treatment of breast cancer with limited therapeutic index, extreme gastric adverse effects and bone marrow suppression. The purpose of the present study was preparation of a dual targeted delivery system of MMC for targeting CD44 and LHRH overexpressed receptors of breast cancer. METHODS: MMC loaded LHRH targeted chonderosome were prepared by precipitation method and were characterized for their physicochemical properties. Cell cycle arrest and cytotoxicity tests were studied on cell lines of MCF-7, MDA-MB231 and 4T1 (as CD44 and LHRH positive cells) and BT-474 cell line (as CD44 negative receptor cells). The in vivo histopathology and antitumor activity of MMC-loaded chonderosomes were compared with free MMC in 4T1 cells induced breast cancer in Balb-c mice. RESULTS: MMC loaded LHRH targeted chonderosomes caused 3.3 and 5.5 fold more cytotoxicity on MCF-7 and 4T1 cells than free MMC at concentrations of 100microM and 10microM, respectively. However, on BT-474 cells the difference was insignificant. The cell cycle test showed no change for MMC mechanism of action when it was loaded in chonderosomes comparing to free MMC. The in vivo antitumor studies showed that MMC loaded LHRH targeted chonderosomes were 6.5 fold more effective in reduction of tumor volume than free MMC with the most severe necrosis compared to non-targeted chonderosomes in pathological studies on harvested tumors. CONCLUSION: The developed MMC loaded LHRH targeted chonderosomes were more effective in tumor growth suppression and may be promising for targeted delivery of MMC in breast cancer.