Multifunctional Nanoplatform Based on Gelatin Nanoparticles with Immunomodulatory Capabilities for Combined Immunotherapy and Chemotherapy of Melanoma.

Tumor immunotherapy has shown considerable therapeutic potential, especially when combined with chemotherapy. In this study, we developed a multifunctional nanoplatform GNPs-DOX/R848 that combined immunotherapy and chemotherapy for the treatment of melanoma, in which gelatin nanoparticles (GNPs) were loaded with the immunomodulatory agent resiquimod (R848) and the chemotherapy drug doxorubicin (DOX). GNPs possessed inherent immunomodulatory properties; when combined with R848, they induced a more pronounced polarization of M1-like macrophages by activating the NF-κB signaling pathway, thereby reversing the immunosuppressive tumor microenvironment. Meanwhile, GNPs effectively delivered R848 and DOX to tumor cells, promoting stronger therapeutic effects of the drugs, which strongly induced the immunogenic cell death triggered by DOX, leading to the infiltration of T cells into the tumor tissue. The treatment of melanoma demonstrated that GNPs-DOX/R848 significantly reduced tumor volume, enhanced the therapeutic effects of chemotherapy, providing a new approach for the combined treatment of cancer with immunotherapy and chemotherapy.