Macrophage membrane-camouflaged nanoparticles as emerging therapeutics in metabolic dysfunction-associated steatotic liver disease

Abstract

Chronic liver disease (CLD) is a major global health burden, with metabolic dysfunction-associated steatotic liver disease (MASLD) as a primary contributor through its promotion of persistent inflammation, fibrotic transformations, and increased cancer risk. Current therapeutic strategies remain inadequate due to poor pharmacokinetics and off-target toxicity, underscoring the need for more targeted and safer treatment options. Macrophages, as key components of the innate immune system, play a central role in liver homeostasis and inflammation, critically shape disease progression and thus represent a compelling therapeutic target. Advances in nanomedicine have led to the development of macrophage membrane–camouflaged nanoparticles (MMNPs), which offer immune-evasive and inflammation-targeting properties conferred by the macrophage membrane. Given the major involvement of macrophages throughout the course of CLD and the superior immunomodulatory properties of their membrane, MMNPs provide a promising and innovative strategy for CLD therapy. This review provides a comprehensive overview of MASLD-associated CLD pathology with a particular focus on the role of macrophages in disease progression. It further explores the characteristics, function-ality, and liver-targeting modifications of MMNPs, highlighting their potential in modulating key pathways to remodel inflammatory environment and reverse liver fibrosis. Finally, existing challenges and future prospects of MMNP-based therapies are discussed, including strategies for enhancing therapeutic efficacy through combination approaches and bioengineering advancements.