A Nonanuclear Pd-Based Coordination Cage Featuring Ni-Chelated Porphyrin Ligand for Cancer Therapy via Combination of Chemodynamic and Photodynamic Modalities

Reactive oxygen species (ROS)-mediated cancer therapy has attracted extensive attention due to its high spatiotemporal selectivity and minimum side-effects. Herein, we report a nonanuclear Pd-based coordination cage of Pd6-TMPP(Ni), constructed from Ni-chelated TMPP(Ni) as the metalloligand and Pd2+ ions (H2TMPP = meso-tetrakis (6-methylpyridin-3-yl) porphyrin). Pd6-TMPP(Ni) integrates dual ROS-generation for cancer therapy, viz., hydroxyl radical (•OH) production and photoinduced singlet oxygen (1O2) generation. In vitro cytotoxicity assays against cancer cell lines NCI-H82 (lung cancer), A549 (lung cancer), KYSE-510 (esophageal cancer), and Te-1 (esophageal cancer), reveal its potent dark toxicity (IC₅₀: 1.867–2.107 μmol L−1) and phototoxicity (IC₅₀: 0.835–1.528 μmol L−1), which is attributed to enhanced intracellular ROS accumulation. This work develops a versatile therapeutic platform that harnesses Ni-induced •OH for chemodynamic therapy (CDT) and porphyrin-generated ¹O₂ for photodynamic therapy (PDT), thereby mitigating the oxygen dependence of conventional PDT.