Inflammatory Macrophages Lysate-based Macroporous Hydrogel for Effective Immunomodulation to Inhibit Tumor Progression, Recurrence and Metastasis

Abstract

Abstract Background Pro-inflammatory M1 macrophages possess the ability to change immunosuppressive tumor microenvironment by releasing various inflammatory factors simultaneously, which can effectively inhibit tumor progression and relapse. However, the risk of cytokines storm caused by the proliferation and excessive activation of M1 macrophages greatly limits it as a biosafety therapeutic strategy in anti-tumor immunotherapy. Therefore, how to engineer natural M1 macrophage to biocompatible biomaterial that maintains the duration time of tumor suppressive property duration time still remains a huge challenge. Methods Here, we sought to develop an injectable macroporous hydrogel (M1LMH) and a small amount of oxaliplatin (OXA) was encapsulated into M1LMH to improve the efficiency of anti-tumor immunotherapy. Results M1MLH-100 had excellent biocompatibility for normal cells and tumor cells, but it could repolarize anti-inflammatory M2 macrophages to pro-inflammatory M1 macrophages via NF-κB and P38/MAPK pathway, thus promoting tumor cells death. M1LMH-100 also could improve the immunogenicity of tumor cells, induce the maturation of BMDCs, and active specific cytotoxicity T cells through the synergistic effect of released inflammatory factors simultaneously. Furthermore, OXA+M1LMH-100 could rapidly release OXA to induce ICD to increase the tumor antigens. OXA+M1LMH-100 could remodel immune microenvironment, thus inhibiting tumor growth, recurrence, and metastasis. Conclusions We expect our findings will be an effective and safe tool to activate tumor-associated immune cells in a spatiotemporal manner, improving the efficiency of anti-tumor immunotherapy.