Immunomodulatory hybrid bio-nanovesicle for self-promoted photodynamic therapy

Thylakoid(Tk)membranes are of unique superiority in photodynamic therapy(PDT)because they not only carry abundant chlorophylls containing photosensitizer porphyrin but also can produce O_(2).However,the current therapeutic performance of Tk is dramatically limited because of their poor tumor targeting and inefficient O_(2) production.Here,we report an immunomodulatory bio-nanovesicle of Tk membranes fused with M1 macrophage-derived extracellular vesicles(M1 EV)for efficient PDT of tumors.The hybrid nanovesicle Tk@M1 was prepared by squeezing the Tk membranes of spinach with M1 EV.The systemic study confirmed that Tk@M1 can not only actively accumulate in tumors but also effectively regulate the inactive immune microenvironment of tumors.Such activated"hot"tumors significantly enhance the PDT efficacy of Tk@M1 attributed to the increased O_(2) from catalase catalyzed decomposition of augmented H_(2)O_(2),providing a novel idea about constructing natural systems for effective tumor treatment.

Natural killer cell-derived extracellular vesicle significantly enhanced adoptive T cell therapy against solid tumors via versatilely immunomodulatory coordination

Insufficient tumor tropism,MHC classⅠmolecules(MHC-I)defects of tumor cells,and immunosuppressive tumor microenvironment(TME)seriously imperil the efficacy of adoptive T cell therapy on solid tumors.Here,natural killer cell-derived extracellular vesicle(Nev)is used as a versatile toolkit to synergistically improve adoptive T cell therapy for solid tumors.Specifically,Nev is modified with dibenzocyclooctynes(DBCO)linked with p H-sensitive benzoic-imine bonds;meanwhile,cytotoxic T lymphocyte(CTL)is decorated with azide groups.Then CTL is armed with Nev(CTL-Nev)through the click chemistry reaction.After systematic administration,Nev obviously promotes the tumor-targeting accumulation of CTL coming from its native tumor-tropism capability.Then,the cleavage of benzoic-imine bonds in the slightly acidic TME leads to the release of Nev,which not only directly induces tumor apoptosis but also promotes the action of CTL via multiplex pathways,such as up-regulating the MHC-I expression on tumor cells,reprogramming tumor-associated macrophages from pro-tumoral M2 phenotypes to tumoricidal M1 phenotypes.The all-around coordination of Nev with CTL results in potent tumor repression.