Nucleus-Targeted Organoiridium-Albumin Conjugate for Photodynamic Cancer Therapy

Angew Chem Int Ed Engl. 2019 Feb 18;58(8):2350-2354. doi: 10.1002/anie.201813002. Epub 2019 Jan 21.

Abstract

An organoiridium-albumin bioconjugate (Ir1-HSA) was synthesized by reaction of a pendant maleimide ligand with human serum albumin. The phosphorescence of Ir1-HSA was enhanced significantly compared to parent complex Ir1. The long phosphorescence lifetime and high 1 O2 quantum yield of Ir1-HSA are highly favorable properties for photodynamic therapy. Ir1-HSA mainly accumulated in the nucleus of living cancer cells and showed remarkable photocytotoxicity against a range of cancer cell lines and tumor spheroids (light IC50 ; 0.8-5 μm, photo-cytotoxicity index PI=40-60), while remaining non-toxic to normal cells and normal cell spheroids, even after photo-irradiation. This nucleus-targeting organoiridium-albumin is a strong candidate photosensitizer for anticancer photodynamic therapy.

Keywords: albumin; organoiridium; photodynamic therapy; photosensitizers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Nucleus / drug effects*
  • Cell Proliferation / drug effects
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Iridium / chemistry
  • Iridium / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Optical Imaging
  • Photochemotherapy*
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Serum Albumin, Human / chemistry
  • Serum Albumin, Human / metabolism*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Photosensitizing Agents
  • Iridium
  • Serum Albumin, Human