Chimeric apoptotic bodies functionalized with natural membrane and modular delivery system for inflammation modulation.

Engineered extracellular vesicles (EVs) carrying therapeutic molecules are promising candidates for disease therapies. Yet, engineering EVs with optimal functions is a challenge that requires careful selection of functionally specific vesicles and a proper engineering strategy. Here, we constructed chimeric apoptotic bodies (cABs) for on-demand inflammation modulation by combining pure membrane from apoptotic bodies (ABs) as a bioconjugation/regulation module and mesoporous silica nanoparticles (MSNs) as a carrier module. MSNs were preloaded with anti-inflammatory agents (microRNA-21 or curcumin) and modified with stimuli-responsive molecules to achieve accurate cargo release at designated locations. The resulting cABs actively target macrophages in the inflammatory region and effectively promote M2 polarization of these macrophages to modulate inflammation due to the synergistic regulatory effects of AB membranes and the intracellular release of preloaded cargos. This work provides strategies to arbitrarily engineer modular EVs that integrate the advantages of natural EVs and synthetic materials for various applications.