Self-generated double-stranded RNA for enhancing tumor immunotherapy and metastasis inhibition

Insufficient activation of the anti-tumor immune response generally limits the efficacy of immunotherapy in malignant tumors. However, efficiently activating anti-tumor cellular and humoral immune response remains an awkward challenge. Here, we reported a self-generation strategy to prepare a versatile double-stranded RNA (dsRNA)-loaded nanovesicular system (NVdsRNA). This nanovesicular system can stimulate dendritic cells activation by delivering tumor antigens and dsRNA (immune adjuvant), thereby stimulating T cell-mediated anti-tumor immune response. In addition, NVdsRNA also polarize macrophages from M2-type to M1-type, which can relieve the immunosuppressive tumor microenvironment in malignant tumor model and activate anti-tumor humoral immune response by antigen-presentation with M1-type macrophages. Of note, this NVdsRNA efficiently extend survival period of melanoma tumor-bearing mice and inhibit triple-negative breast tumor metastasis. In addition, NVdsRNA combined with interleukin-12 improve the synergistic tumor immunotherapy. Collectively, our work offers a self-generation strategy to prepare a versatile nanovesicular system for synergistically activating anti-tumor cellular and humoral immune response to achieve effective tumor immunotherapy and metastasis inhibition.