Photothermal Therapy Nanomaterials Boosting Transformation of Fe(III) into Fe(II) in Tumor Cells for Highly Improving Chemodynamic Therapy

Abstract

Chemodynamic therapy based on Fe²⁺-catalyzed Fenton reaction holds great promise in cancer treatment. However, low-produced hydroxyl radicals in tumor cells constitute its severe challenges because of the fact that Fe²⁺ with high catalytic activity could be easily oxidized into Fe³⁺ with low catalytic activity, greatly lowering Fenton reaction efficacy. Here, we codeliver CuS with the iron-containing prodrug into tumor cells. In tumor cells, the overproduced esterase could cleave the phenolic ester bond in the prodrug to release Fe²⁺, activating Fenton reaction to produce the hydroxyl radical. Meanwhile, CuS could act as a nanocatalyst for continuously catalyzing the regeneration of high-active Fe²⁺ from low-active Fe³⁺ to produce enough hydroxyl radicals to efficiently kill tumor cells as well as a photothermal therapy agent for generating hyperthermia for thermal ablation of tumor cells upon NIR irradiation. The results have exhibited that the approach of photothermal therapy nanomaterials boosting transformation of Fe³⁺ into Fe²⁺ in tumor cells can highly improve Fenton reaction for efficient chemodynamic therapy. This strategy was demonstrated to have an excellent antitumor activity both in vitro and in vivo, which provides an innovative perspective to Fenton reaction-based chemodynamic therapy.