Preparation, structure, cytotoxicity and mechanism of action of ferritin-Pt(II) terpyridine compound nanocomposites

Nanomedicine (Lond). 2018 Dec;13(23):2995-3007. doi: 10.2217/nnm-2018-0259. Epub 2018 Dec 3.

Abstract

Aim: A Pt(II)-terpyridine compound, bearing two piperidine substituents at positions 2 and 2' of the terpyridine ligand (1), is highly cytotoxic and shows a mechanism of action distinct from cisplatin. 1 has been incorporated within the ferritin nanocage (AFt).

Materials & methods: Spectroscopic and crystallographic data of the Pt(II)-AFt nanocomposite have been collected and in vitro anticancer activity has been explored using cancer cells.

Results: Pt(II)-containing fragments bind His49, His114 and His132. Pt(II)-AFt nanocomposite is less cytotoxic than 1, but it is more toxic than cisplatin at high concentrations. The Pt(II)-AFt nanocomposite triggers necrosis in cancer cells, as free 1 does.

Conclusion: Pt(II)-AFt nanocomposites are promising vehicles to deliver Pt-based drugs to cancer cells.

Keywords: Pt(II)-terpyridine compounds; platinum-based drug; protein metalation; protein nanocage; protein–metallodrug interactions.

MeSH terms

  • Amino Acid Sequence
  • Amino Acids / chemistry
  • Antineoplastic Agents / chemistry*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cisplatin / adverse effects
  • Cisplatin / pharmacology*
  • Drug Carriers / chemistry*
  • Drug Design
  • Drug Liberation
  • Ferritins / chemistry*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Nanocomposites / chemistry*
  • Particle Size
  • Piperidines / chemistry
  • Protein Binding
  • Signal Transduction
  • Structure-Activity Relationship
  • Surface Properties

Substances

  • Amino Acids
  • Antineoplastic Agents
  • Drug Carriers
  • Piperidines
  • piperidine
  • Ferritins
  • Cisplatin