1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine and Breast-Neoplasms

A lipid-cisplatin conjugate was synthesized for super-molecular assembly with lipids to form a new generation of liposomal cisplatin formulation, lipocisplatin. In vitro, lipocisplatin has higher efficacy in human ovarian cancer A2780 and human breast cancer MCF-7 with the murine breast cancer cell line 4T1 which is currently an established model for stage IV breast cancer as the most sensitive strain. Moreover, lipocisplatin demonstrated a greater MTD value and relatively longer blood circulation as compared to cisplatin. Lipocisplatin preferentially accumulate drugs to the tumor site, resulting in a better tumor inhibition efficacy. Moreover, lipocisplatin exceeds the size cutoff for kidney clearance, hence it bypasses the nephrotoxicity of cisplatin which is a major curse of one of the most efficient anticancer drugs nowadays in clinic. The results here indicated lipocisplatin may be translated into a new generation of liposomal based cisplatin drug in clinic.

Topics: Animals; Breast Neoplasms; Cell Death; Cell Line, Tumor; Cisplatin; DNA Adducts; Dose-Response Relationship, Drug; Endocytosis; Female; Humans; Kidney; Lipids; Mammary Neoplasms, Animal; Maximum Tolerated Dose; Mice, Inbred BALB C; Phospholipid Ethers; Tissue Distribution; Treatment Outcome