Background: Mitomycin C (MMC) is an anti-cancer drug used for the treatment of breast cancer
with limited therapeutic index, extreme gastric adverse effects and bone marrow suppression. The purpose of the
present study was the 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 was prepared by precipitation method and was 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 inducing 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 100μM and 10μM, 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 compared to free MMC. The in vivo antitumor studies showed that MMC loaded LHRH
targeted chonderosomes were 6.5 fold more effective in the 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.