Atherosclerosis is the most common cause of cardiovascular diseases that contribute to the major morbidity worldwide, but still lacking of effective treatment strategy. Here, a hybrid cell is constructed for the sonodynamic effect promoted cell therapy of early atherosclerosis by fusing M2 macrophages with thylakoid (TK) membranes. After systemic administration, the obtained TK-M2 actively accumulates in the early atherosclerotic plaques, wherein M2 macrophages relieve the cholesterol accumulation and the inflammation in the foam cells. Meanwhile, the TK membranes decorated on the M2 macrophages exhibit both type I and type II sonodynamic effects under ultrasound (US) activation, inducing the direct apoptosis of foam cells. The cooperation of M2 and TK leads to significant outcome in eliminating atherosclerotic plaques without obvious side-effects, providing a new avenue for atherosclerosis treatment.

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.