Nanoformulations of a potent copper-based aquaporin inhibitor with cytotoxic effect against cancer cells

Nanomedicine (Lond). 2016 Jul;11(14):1817-30. doi: 10.2217/nnm-2016-0086. Epub 2016 Jul 7.

Abstract

Aim: Development of liposomal formulations of Cuphen, a potent copper-based aquaporin inhibitor with therapeutic potential against melanoma and colon cancer.

Materials & methods: Cuphen was incorporated into liposomes using the dehydration-rehydration method. The ability of Cuphen to induce cancer cell death was evaluated by MTS and ViaCount assays. In vivo toxicity studies were performed in BALB/c mice.

Results: In vitro studies illustrated the antiproliferative effects of Cuphen in different cancer cell lines, in free form or after incorporation into liposomes. In vivo studies revealed no toxic effects after parenteral administration of Cuphen liposomes.

Conclusions: Cuphen liposomes are highly attractive to be further tested in murine models due to the possibility of stabilizing and specifically deliver this metallodrug to tumor sites.

Keywords: Cuphen; aquaporins; colon cancer; cytotoxic effect; in vivo toxicity studies; liposomes; melanoma; metallodrugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Aquaporins / antagonists & inhibitors*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Colonic Neoplasms / drug therapy
  • Coordination Complexes / administration & dosage*
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Copper / administration & dosage*
  • Copper / chemistry
  • Copper / pharmacology*
  • Humans
  • Liposomes
  • Male
  • Melanoma / drug therapy
  • Mice, Inbred BALB C
  • Phenanthrolines / administration & dosage
  • Phenanthrolines / chemistry
  • Phenanthrolines / pharmacology

Substances

  • Antineoplastic Agents
  • Aquaporins
  • Coordination Complexes
  • Liposomes
  • Phenanthrolines
  • Copper
  • 1,10-phenanthroline