Pd‐Single‐Atom Coordinated Biocatalysts for Chem‐/Sono‐/Photo‐Trimodal Tumor Therapies

The diversity, complexity, and heterogeneity of malignant tumor seriously undermine the efficiency of mono‐modal treatment. Recently, multi‐modal therapeutics with enhanced antitumor efficiencies have attracted increasing attention. However, designing a nanotherapeutic platform with uniform morphology in nanoscale that integrates with efficient chem‐/sono‐/photo‐trimodal tumor therapies is still a great challenge. Here, new and facile Pd‐single‐atom coordinated porphyrin‐based polymeric networks as biocatalysts, namely, Pd‐Pta/Por, for chem‐/sono‐/photo‐trimodal tumor therapies are designed. The atomic morphology and chemical structure analysis prove that the biocatalyst consists of atomic Pd‐N coordination networks with a Pd‐N2‐Cl2 catalytic center. The characterization of peroxidase‐like catalytic activities displays that the Pd‐Pta/Por can generate abundant •OH radicals for chemodynamic therapies. The ultrasound irradiation or laser excitation can significantly boost the catalytic production of 1O2 by the porphyrin‐based sono‐/photosensitizers to achieve combined sono‐/photodynamic therapies. The superior catalytic production of •OH is further verified by density functional theory calculation. Finally, the corresponding in vitro and in vivo experiments have demonstrated their synergistic chem‐/sono‐/photo‐trimodal antitumor efficacies. It is believed that this study provides new promising single‐atom‐coordinated polymeric networks with highly efficient biocatalytic sites and synergistic trimodal therapeutic effects, which may inspire many new findings in reactive oxygen species‐related biological applications across broad therapeutics and biomedical fields. A precisely designed Pd single‐atom coordinated biocatalyst (Pd‐Pta/Por) is synthesized for achieving chem‐/sono‐/photo‐trimodal dynamic tumor therapies. Experimental results and theoretical calculations demonstrate that the Pd‐Pta/Por biocatalyst consists of atomic Pd‐N coordination active sites and has efficient catalytic yield of reactive oxygen species (ROS) for highly synergistic antitumor therapies, which takes an essential step toward developing ROS‐related therapeutic and biological applications.