Arsenoplatin-Ferritin Nanocage: Structure and Cytotoxicity

Int J Mol Sci. 2021 Feb 13;22(4):1874. doi: 10.3390/ijms22041874.

Abstract

Arsenoplatin-1 (AP-1), the prototype of a novel class of metallodrugs containing a PtAs(OH)2 core, was encapsulated within the apoferritin (AFt) nanocage. UV-Vis absorption spectroscopy and inductively coupled plasma-atomic emission spectroscopy measurements confirmed metallodrug encapsulation and allowed us to determine the average amount of AP-1 trapped inside the cage. The X-ray structure of AP-1-encapsulated AFt was solved at 1.50 Å. Diffraction data revealed that an AP-1 fragment coordinates the side chain of a His residue. The biological activity of AP-1-loaded AFt was comparatively tested on a few representative cancer and non-cancer cell lines. Even though the presence of the cage reduces the overall cytotoxicity of AP-1, it improves its selectivity towards cancer cells.

Keywords: As compounds; Pt compounds; anti-cancer activity; ferritin encapsulation; metal complexes; metallodrugs; protein metalation.

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Arsenic Trioxide / analogs & derivatives*
  • Arsenic Trioxide / chemistry
  • Arsenic Trioxide / pharmacology
  • BALB 3T3 Cells
  • Cisplatin / analogs & derivatives*
  • Cisplatin / chemistry
  • Cisplatin / pharmacology
  • Cytotoxins* / chemistry
  • Cytotoxins* / pharmacology
  • Ferritins* / chemistry
  • Ferritins* / pharmacology
  • Humans
  • Mice
  • Molecular Structure
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Platinum Compounds* / chemistry
  • Platinum Compounds* / pharmacology
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Cytotoxins
  • Platinum Compounds
  • arsenoplatin-1
  • Ferritins
  • Cisplatin
  • Arsenic Trioxide