Immunomodulatory hydrogel neutralizes tumor acidity to augment immune responses for the prevention of post-surgical recurrence of melanoma

Post-resection recurrence remains a severe problem in melanoma treatment. New therapeutic strategies, such as chemodynamic therapy (CDT), exhibit high specificity and responsiveness, demonstrating potential to elicit antitumor immune responses by triggering immunogenic cell death (ICD). However, the efficacy of CDT still faces challenges from the immunosuppressive tumor microenvironment (TME) characterized by elevated lactate levels. Herein, we propose a strategy to construct an immunomodulatory hydrogel to synergistically reprogram tumor-associated macrophages and amplify ICD to inhibit melanoma recurrence after surgery. The hyaluronic acid hydrogel containing borosilicate glasses (BGs) and Fe₃O₄ nanoparticles (HBF hydrogel) are obtained, which can neutralize tumor acidity to reprogram macrophages to M1 phenotype. Furthermore, the HBF hydrogel induces reactive oxygen species production in melanoma cells, which could induce ICD through CDT and stimulate strong antitumor immune responses, thereby promoting tumor immunotherapy. The cooperative ICD induced by CDT and immunosuppressive TME remodeling leads to effective suppression of tumor recurrence. This work provides a promising strategy for immunomodulation-enhanced melanoma therapy through the fabrication of hydrogel to prevent postsurgical tumor recurrence.