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

Abstract

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.