Cisplatin-loaded metal-phenolic network with photothermal-triggered ROS generation for chemo-photothermal therapy of cancer

Developing multifunctional composites has received widespread attention for cancer treatment. Herein, a metal-phenolic network (MPN)-based composite loading with chemotherapy agents (TAFP) exhibits high anti-tumor therapeutic efficacy via photothermal therapy (PTT), chemo-dynamic therapy (CDT), and chemotherapy. The nanocomposite was formed by mixing the chemotherapeutic drugs (cisplatin, DDP) into the tannic acid (TA) and Fe3+ network (TAFe) to integrate the synergistic effect of PTT, CDT, and chemotherapy. Due to the acidic tumor microenvironment, the active substances could be released with the degradation of the metal-phenolic network, and the released DDP would induce the chemotherapy. More importantly, the released TA under the acidic environment could increase iron bioavailability by converting Fe3+ to Fe2+, which converts hydrogen peroxide (H2O2) to highly toxic hydroxyl radical via the Fenton reaction. Meanwhile, the heat generated from TAFP after near-infrared (NIR) laser irradiation could enhance the therapeutic effect of CDT and chemotherapy. Furthermore, the composite exhibited unique anticancer efficacy in vivo with low toxicity. Collectively, this work may facilitate the development of metal-phenolic network-based photothermal agents for clinic anti-tumor applications.