Macrophage-Derived Nanosponges Adsorb Cytokines and Modulate Macrophage Polarization for Renal Cell Carcinoma Immunotherapy.

Renal cell carcinoma (RCC) is a hot tumor infiltrated by large numbers of CD8 + T cells and is highly sensitive to immunotherapy. However, tumor-associated macrophages (TAMs), mainly M2 macrophages, tend to undermine the efficacy of immunotherapy and promote the progression of RCC. Here, we fabricated macrophage-derived nanosponges by M2 macrophage membrane-coated PLGA, which could chemotaxis to the CXC and CC chemokine subfamily-enriched RCC microenvironment via corresponding membrane chemokine receptors. Subsequently, the nanosponges acted like cytokine decoys to adsorb and neutralize broad-spectrum immunosuppressive cytokines such as CSF-1, TGF-β, and IL-10, thereby reversing the polarization of M2-TAMs toward the pro-inflammatory M1 phenotype, and enhancing the anti-tumor effect of CD8 + T cells. To further enhance the polarization reprogramming efficiency of TAMs, we conjugated DSPE-PEG-M2pep on the surface of macrophage-derived nanosponges for specific recognition of M2-TAMs, and encapsulated the TLR7/8 agonist, R848, in these nanosponges to induce M1 polarization, which resulted in significant efficacy against RCC. In addition, these nanosponges exhibited undetectable biotoxicity, making them suitable for clinical applications. In summary, we provide a promising and facile strategy for immunomodulatory therapies, which are expected to be used in the treatment of tumors, autoimmune diseases, and inflammatory diseases. This article is protected by copyright. All rights reserved.