The effect of lipocisplatin on cisplatin efficacy and nephrotoxicity in malignant breast cancer treatment

Biomaterials. 2014 Aug;35(24):6462-72. doi: 10.1016/j.biomaterials.2014.04.023. Epub 2014 May 3.

Abstract

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.

Keywords: Breast cancer; Cisplatin; Liposome; Nanoparticles; Nephrotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacokinetics
  • Cisplatin / therapeutic use*
  • Cisplatin / toxicity*
  • DNA Adducts / metabolism
  • Dose-Response Relationship, Drug
  • Endocytosis / drug effects
  • Female
  • Humans
  • Kidney / drug effects
  • Kidney / pathology*
  • Lipids / chemical synthesis
  • Lipids / chemistry
  • Mammary Neoplasms, Animal / drug therapy*
  • Mammary Neoplasms, Animal / pathology
  • Maximum Tolerated Dose
  • Mice, Inbred BALB C
  • Phospholipid Ethers / chemical synthesis
  • Phospholipid Ethers / chemistry
  • Tissue Distribution / drug effects
  • Treatment Outcome

Substances

  • 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine
  • DNA Adducts
  • Lipids
  • Phospholipid Ethers
  • Cisplatin