A metal–phenolic network-based multifunctional nanocomposite with pH-responsive ROS generation and drug release for synergistic chemodynamic/photothermal/chemo-therapy

Developing multifunctional nanomaterials with chemodynamic therapy (CDT)-based combination therapy has increasingly become a promising strategy for cancer treatment. Herein, a metal-phenolic network-based multifunctional nanocomposite (PID@Fe-TA) via the noncovalent interaction of multiple nontoxic raw materials has been designed to integrate the synergistic effect of CDT, photothermal therapy (PTT) and chemotherapy into one nanoplatform for breast cancer treatment. Benefiting from the pH-responsive properties and the assistance of near infrared (NIR) laser irradiation, the outer shell Fe³⁺-tannic acid (TA) complexes of PID@Fe-TA can be easily degraded into Fe³⁺ and TA as well as to release chemotherapeutic drugs (doxorubicin, DOX) and photothermal transforming agents (indocyanine green, ICG) in a tumor microenvironment (TME) or cancer cells. The released TA can accelerate the reduction of Fe³⁺ to Fe²⁺ for ensuring effective conversion of hydrogen peroxide (H₂O₂) into a highly toxic hydroxyl radical (˙OH) via the Fenton reaction. The exposed DOX can enter the cell nucleus to induce chemotherapy. The released ICG can locate the distribution of nanocomposites in the body. Besides, the heat generated from PID@Fe-TA after NIR laser irradiation can further promote the therapeutic effect of PPT-enhanced CDT. Importantly, an excellent therapeutic efficacy is achieved both in in vitro and in vivo via the CDT/PTT/chemotherapy combination based on this "all-in-one" nanoplatform, providing a good paradigm for effective cancer eradication.