Apoptotic body based biomimetic hybrid nanovesicles to attenuate cytokine storms for sepsis treatment

Abstract

Sepsis is a severe immune response to pathogens that causes high mortality with limited treatment options. It is characterized by the hyperactivation of macrophages and cytokine storms. Given the anti-inflammatory properties of M2 macrophages derived apoptotic bodies (AB) and their specific uptake by macrophages, a novel approach is employed to combine AB with artificial liposomes to create apoptotic body based biomimetic hybrid nanovesicles (L-AB). The L-AB effectively inherit "eat me" signaling molecules on the surface of the AB, facilitating their targeted uptake by macrophages in both in vitro and in vivo settings. Utilizing this mechanism for the delivery of dexamethasone demonstrates efficient distribution of the drug to inflammatory tissues in septic mice, where it is selectively internalized by macrophages, thereby mitigating excessive macrophage activation and tissue damage, and ultimately increasing the survival rate of septic mice. Taken together, the apoptotic body biomimetic nanovesicles represent a potentially drug delivery system capable of specifically targeting macrophages for the treatment of sepsis.