Reprogramming Dysfunctional\nDendritic Cells by a Versatile\nCatalytic Dual Oxide Antigen-Captured Nanosponge for Remotely Enhancing\nLung Metastasis Immunotherapy

Dendritic cells (DCs) play a crucial role in initiating\nantitumor\nimmune responses. However, in the tumor environment, dendritic cells\noften exhibit impaired antigen presentation and adopt an immunosuppressive\nphenotype, which hinders their function and reduces their ability\nto efficiently present antigens. Here, a dual catalytic oxide nanosponge\n(DON) doubling as a remotely boosted catalyst and an inducer of programming\nDCs to program immune therapy is reported. Intravenous delivery of\nDON enhances tumor accumulation via the marginated target. At the\ntumor site, DON incorporates cerium oxide nanozyme (CeO<sub>2</sub>)-coated iron oxide nanocubes as a peroxide mimicry in cancer cells,\npromoting sustained ROS generation and depleting intracellular glutathione,\ni.e., chemodynamic therapy (CDT). Upon high-frequency magnetic field\n(HFMF) irradiation, CDT accelerates the decomposition of H<sub>2</sub>O<sub>2</sub> and the subsequent production of more reactive oxygen\nspecies, known as Kelvin’s force laws, which promote the cycle\nbetween Fe<sup>3+</sup>/Fe<sup>2+</sup> and Ce<sup>3+</sup>/Ce<sup>4+</sup> in a sustainable active surface. HFMF-boosted catalytic\nDON promotes tumors to release tumor-associated antigens, including\nneoantigens and damage-associated molecular patterns. Then, the porous\nDON acts as an antigen transporter to deliver autologous tumor-associated\nantigens to program DCs, resulting in sustained immune stimulation.\nCatalytic DON combined with the immune checkpoint inhibitor (anti-PD1)\nin lung metastases suppresses tumors and improves survival over 40\ndays.