Ruthenium complex delivery using liposomes to improve bioactivity against HeLa cells via the mitochondrial pathway

Nanomedicine (Lond). 2018 Nov;13(22):2851-2866. doi: 10.2217/nnm-2018-0236. Epub 2018 Nov 20.

Abstract

Aim: The aim of this study was to encapsulate a ruthenium complex [Ru(ttbpy)2PIP](ClO4)2 (Ru) in liposomes to enhance their antitumor effect on human cervical cancer.

Methods: The Ru-loaded PEGylated liposomes (Ru-Lip) were prepared using thin-film hydration method. The mechanism of action was studied.

Results: A novel Ru was successfully synthesized. Ru-Lip showed stronger cytotoxic activity against HeLa cells than Ru. Ru-Lip demonstrated a more significant increase in apoptosis, reactive oxygen species production and apoptosis-associated processes (intracellular calcium concentration, cytochrome c release and activation of Bax and caspase-3) than Ru. Ru-Lip exhibited greater blockade efficacy in the cell cycle G1 phase and greater DNA damage than Ru.

Conclusion: Ru-Lip significantly elevates the anticancer effect via reactive oxygen species-mediated mitochondrial dysfunctional pathway.

Keywords: anticancer activity; apoptosis; liposomes; mitochondria; ruthenium complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Apoptosis / drug effects
  • Biological Transport
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Drug Carriers / chemistry*
  • HeLa Cells
  • Humans
  • Ligands
  • Liposomes / chemistry
  • Mitochondria / metabolism*
  • Reactive Oxygen Species / chemistry
  • Ruthenium / chemistry*
  • Signal Transduction

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Drug Carriers
  • Ligands
  • Liposomes
  • Reactive Oxygen Species
  • Ruthenium