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

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 due to that Fe2+ with high catalytic activity could be easily oxidized into Fe3+ with low catalytic activity, greatly lowering Fenton reaction efficacy. Here, we co-deliver CuS with iron-containing prodrug into tumor cells. In tumor cells, the overproduced esterase could cleave phenolic ester bond in prodrug to release Fe2+, activating Fenton reaction to produce 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 radical 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 anti-tumor activity both in vitro and in vivo, which provides an innovative perspective to Fenton reaction based chemodynamic therapy.