A novel biomimetic liposome drug delivery system mediated by macrophage targeting for precision treatment of encephalitis

Abstract The highly selective and defensive properties of the blood‐brain barrier (BBB) significantly hinder effective drug penetration and therapeutic efficacy, presenting significant challenges for treating central nervous system (CNS) disorders, particularly neuroinflammatory diseases. In this study, we innovatively developed a macrophage‐mediated biomimetic liposomal drug delivery system (AC‐LP@RAW) co‐loaded with curcumin (Cur) and gold nanoclusters (AuNCs) for targeted therapy of acute encephalitis. By leveraging the unique immune homing properties of RAW 264.7 cells (RAW), AC‐LP@RAW demonstrates enhanced BBB penetration and precise targeting to inflammatory sites, significantly improving Cur delivery to brain parenchyma. Near‐infrared (NIR) irradiation‐induced photothermal effects subsequently trigger the disintegration of the system and site‐specific drug release at inflamed regions, exhibiting remarkable capabilities in recognizing acute inflammation and promoting tissue repair. Furthermore, AC‐LP@RAW enables real‐time imaging and monitoring of deep‐brain inflammatory lesions in acute neuroinflammation models. This novel liposomal delivery system demonstrates tremendous potential for overcoming BBB limitations while achieving precise targeted therapy and visual tracking imaging for acute encephalitis.