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

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.