Plant-Derived Exosome-Like Nanovesicles-Created injectable hydrogel for augmented cancer immunotherapy

[Display omitted] •Plant-derived exosome-like nanovesicles were designed as gelators to construct injectable hydrogel.•The hydrogel enabled to powerfully regulate the immunosuppressive tumor microenvironment.•The biocompatibility and potent immune-modulating capabilities of the hydrogel were demonstrated.•The hydrogel demonstrated significant inhibition of tumor growth and metastasis, as well as systemic immune response activation. Immunosuppressive tumor microenvironment (TME) poses a significant challenge to cancer immunotherapy. This study presents a robust approach utilizing plant-derived exosome-like nanovesicles (PDENs)-based hydrogel to powerfully regulate the immunosuppressive TME for cascade-amplified therapeutic outcome. PDENs, sourced from edible plants, offer advantages such as wide availability and excellent biocompatibility. The hydrogel is constructed by ginseng-derived exosome-like nanovesicles (GDEN) and spinach-derived exosome-like nanovesicles (SDEN), where SDEN is conjugated with maleimide-modified OVA257-264 peptide (OVA-MaI) to create SDEN@OVA, and both GDEN and SDEN@OVA are chemically engineered as gelators. Upon intratumoral injection, SDEN@OVA within the hydrogel catalyzes oxygen generation, alleviates TME hypoxia and reduces immune suppression while OVA peptide promotes dendritic cells (DCs) maturation and activation of T cells. Simultaneously, GDEN remodels tumor-associated macrophages (TAMs), further reversing immune suppression and enhancing immunotherapy outcomes. These findings highlight the potential of PDENs-based hydrogel as a promising strategy to overcome immunosuppressive TME and boost the efficacy of cancer immunotherapy.