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 1 O2 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.