Magnetocaloric‐Responsive Hydrogel Nanoarchitectonics for Pyroptosis‐Relay‐Immunotherapy to Suppress Post‐Operation Tumor Recurrence and Metastasis

Although a widely used option in contemporary anticancer treatment, surgery still causes serious issues, including post‐operation recurrence and the development of metastases. Immunotherapy, often following surgical resection of a tumor, has demonstrated benefits in improving the therapeutical outcomes of surgery. However, antigen generation and presentation play an essential role in reversing limited T‐cell responses or immunological resistance. Thus, a gelatin‐tannic acid gel (GelTA) crosslinked bimetallic (Zn0.35Fe0.65) magnetocaloric‐responsive hydrogels (GelTAMNPs) are developed to mediate pyroptosis‐relay‐immunotherapy for suppressing post‐operation tumor recurrence and metastasis. After surgical resection of tumor, GelTAMNPs generate hyperthermia inducible by alternating magnetic field and release ions (Fe3+, Fe2+, and Zn2+), reinforcing pyroptosis. Subsequently, the cell contents and cytokines released due to pyroptosis act as a “relay baton” passed from the tumor to the lymph nodes, leading to an enhanced systemic immune response. Combined with the PD‐1 immune checkpoint blockade, the recurrence and metastasis are significantly suppressed. An in vivo preclinical study on B16F10 tumor‐bearing mice demonstrates a long‐lasting immunological activation due to post‐surgical administration of GelTAMNPs. Altogether, the presented hydrogel exhibits a potential high magnetic sensitive pyroptosis‐relay‐immunotherapeutic platform for postoperative adjuvant treatment. (Zn0.35Fe0.65) Fe2O4 hydrogel‐based therapeutic system. The gelatin matrix is crosslinked with tannic acid and designated as GelTA. The GelTA hydrogel conjugated within (Zn0.35Fe0.65) Fe2O4 is reffered to as GelTA‐(Zn0.35Fe0.65) Fe2O4 MNPs (GelTAM) hydrogel. This injectable hydrogel is developed to load magnetic responsive agents to treat recurring neoplasm as well as its metastasis through local implantation.