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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 O2. However, the current therapeutic performance of Tk is dramatically limited because of their poor tumor targeting and inefficient O2 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 O2 from catalase catalyzed decomposition of augmented H2O2, providing a novel idea about constructing natural systems for effective tumor treatment.
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