A highly potent ruthenium(II)-sonosensitizer and sonocatalyst for in vivo sonotherapy

Nat Commun. 2021 Aug 18;12(1):5001. doi: 10.1038/s41467-021-25303-1.

Abstract

As a basic structure of most polypyridinal metal complexes, [Ru(bpy)3]2+, has the advantages of simple structure, facile synthesis and high yield, which has great potential for scientific research and application. However, sonodynamic therapy (SDT) performance of [Ru(bpy)3]2+ has not been investigated so far. SDT can overcome the tissue-penetration and phototoxicity problems compared to photodynamic therapy. Here, we report that [Ru(bpy)3]2+ is a highly potent sonosensitizer and sonocatalyst for sonotherapy in vitro and in vivo. [Ru(bpy)3]2+ can produce singlet oxygen (1O2) and sono-oxidize endogenous 1,4-dihydronicotinamide adenine dinucleotide (NADH) under ultrasound (US) stimulation in cancer cells. Furthermore, [Ru(bpy)3]2+ enables effective destruction of mice tumors, and the therapeutic effect can reach deep tissues over 10 cm under US irradiation. This work paves a way for polypyridinal metal complexes to be applied to the noninvasive precise sonotherapy of cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • NAD / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • Oxidation-Reduction / radiation effects
  • Porphyrins / chemistry
  • Ruthenium / administration & dosage
  • Ruthenium / chemistry*
  • Singlet Oxygen / metabolism
  • Ultrasonic Therapy*
  • Ultrasonic Waves

Substances

  • Antineoplastic Agents
  • Porphyrins
  • NAD
  • Singlet Oxygen
  • Ruthenium