In-vitro and In-vivo Photocatalytic Cancer Therapy with Biocompatible Iridium(III) Photocatalysts

Angew Chem Int Ed Engl. 2021 Apr 19;60(17):9474-9479. doi: 10.1002/anie.202015671. Epub 2021 Mar 17.

Abstract

Photocatalytic anticancer profile of a IrIII photocatalyst (Ir3) with strong light absorption, high turnover frequency, and excellent biocompatibility is reported. Ir3 showed selective photo-cytotoxicity against cisplatin- and sorafenib-resistant cell lines while remaining dormant to normal cell lines in the dark. Ir3 exhibited excellent photo-catalytic oxidation of cellular co-enzyme, the reduced nicotinamide adenine dinucleotide phosphate (NADPH), and amino acids via a single electron transfer mechanism. The photo-induced intracellular redox imbalance and change in mitochondrial membrane potential resulted in necrosis and apoptosis of cancer cells. Importantly, Ir3 exhibited high biocompatibility and photo-catalytic anticancer efficiency as evident from in vivo zebrafish and mouse cancer models. To the best of our knowledge, Ir3 is the first IrIII based photocatalyst with such a high biocompatibility and photocatalytic anticancer therapeutic effect.

Keywords: NADPH; bioinorganic chemistry; metals in medicine; photocatalysis; photodynamic therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Biocompatible Materials / chemical synthesis
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology*
  • Catalysis
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Drug Screening Assays, Antitumor
  • Humans
  • Iridium / chemistry
  • Iridium / pharmacology*
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / pathology
  • Photochemical Processes
  • Photochemotherapy*

Substances

  • Antineoplastic Agents
  • Biocompatible Materials
  • Coordination Complexes
  • Iridium