Composition-Dependent Enzyme Mimicking Activity and Radiosensitizing Effect of Bimetallic Clusters to Modulate Tumor Hypoxia for Enhanced Cancer Therapy

Adv Mater. 2022 Aug;34(31):e2203734. doi: 10.1002/adma.202203734. Epub 2022 Jul 3.

Abstract

Alloying is an efficient chemistry to tailor the properties of metal clusters. As a class of promising radiosensitizers, most previously reported metal clusters exhibit unitary function and cannot overcome radioresistance of hypoxic tumors. Here, atomically precise alloy clusters Pt2 M4 (M = Au, Ag, Cu) are synthesized with bright luminescence and adequate biocompatibility, and their composition-dependent enzyme mimicking activity and radiosensitizing effect is explored. Specifically, only the Pt2 Au4 cluster displays catalase-like activity, while the others do not have clusterzyme properties, and its radiosensitizing effect is the highest among all the alloy clusters tested. By taking advantage of the sustainable production of O2 via the decomposition of endogenous H2 O2 , the Pt2 Au4 cluster modulates tumor hypoxia as well as increases the efficacy of radiotherapy. This work thus advances the cluster alloying strategy to produce multifunctional therapeutic agents for improving hypoxic tumor therapy.

Keywords: alloy clusters; clusterzymes; hypoxia; metal clusters; radiotherapy.

MeSH terms

  • Alloys
  • Humans
  • Hypoxia
  • Neoplasms* / radiotherapy
  • Radiation-Sensitizing Agents* / pharmacology
  • Tumor Hypoxia

Substances

  • Alloys
  • Radiation-Sensitizing Agents