Biodegradable copper telluride nanosheets for redox-homeostasis breaking-assisted chemodynamic cancer therapy boosted by mild-photothermal effect

Abstract

Chemodynamic therapy (CDT) holds great promise for cancer treatment through employing the Fenton or Fenton-like effects for highly toxic ·OH production exclusively in the tumor microenvironment. Herein, glutathione (GSH)-degradable Cu2-xTe nanosheets modified with polyethylene glycol (bioCu2-xTe NSs) as a multifunctional CDT agent are reported for effective cancer treatment via mild-photothermally enhanced CDT. The resulting bioCu2-xTe NSs exhibit excellent near-infrared II (NIR-II) plasmonic absorption and photothermal properties. Upon endocytosis by cancer cells, bioCu2-xTe NSs are degraded into Cu+ and elemental Te by GSH overexpressed in cancer cells. The generated Cu+ and Te together exhibit efficient catalytic decomposition of endogenous H2O2 into ·OH with effective GSH depletion and redox homeostasis breaking of cancer cells. The mild-photothermal effect from the NIR-II irradiation is confirmed to promote intracellular ·OH production and tumor accumulation of bioCu2-xTe NSs. Owing to all these prominent features, our results on both in vitro and in vivo studies verify the remarkable therapeutic efficacy via mild-photothermally enhanced CDT on a MCF-7 tumor mouse model with intravenous administration of bioCu2-xTe NSs under NIR-II irradiation. This study demonstrates the potential of bioCu2-xTe NSs as a potent CDT agent, which features GSH-triggered degradability and excellent therapeutic functions, for efficient cancer treatment.