Engineering of liposomal borrelidin for treatment of metastatic breast cancer

Abstract

Borrelidin is a potent natural antibiotics which has anti-cancer effect and induce apoptosis in endothelial cells. For the treatment of metastasis, borrelidin can be a new drug for targeting both the primary tumor growth inhibition and disruption of neovasculature of tumor tissue. However, borrelidin can induce the side effect in body systemically when the borrelidin itself is injected in the body because a small molecule like borrelidin is easily removed in body through clearance pathways. Therefore, using nanotechnology for cancer therapy, we loaded borrelidin in the biocompatible and biodegradable liposome nanoparticle and optimized its composition by checking the loading efficiency of borrelidin, liposome stability, leakage of borrelidin and tumor accumulation. Then, we checked the inhibition of proliferation of tumor cells and also, anti-angiogenic effect of optimized liposomal borrelidin in vitro and in vivo. Finally, we observed the therapeutic effect in 4T1 primary tumor and lung metastasis model, and compared systemic toxicity of liposomal borrelidin with free borrelidn. In conclusion, we got better therapeutic effect of liposomal borrelidin in primary tumor and lung metastasis than free borrelidin or conventional breast cancer drug doxil. Although the liposomal borrelidin also caused systemic toxicity, it was observed to be short-termed, on the other hand, the free borrelidin caused long term body toxicity in mice.