Muscle-homing peptides modified biomimetic curcumin nanoparticles ameliorate skeletal muscle dysfunction in aging mice.

With increasing age, skeletal muscle gradually loses mass and strength, and the risk of falls and fractures escalates among elderly individuals. Inflammation is closely related to age-related muscle atrophy and is the potential target for treating muscular atrophy. Here, biomimetic curcumin nanoparticles (M12MNCs) are prepared via encapsulating curcumin in the skeletal muscle cell membranes modified via muscle-homing peptides (M12) for the treatment of aging related skeletal muscle atrophy. The M12MNCs have good biocompatibility and can be enriched in aging skeletal muscle. After treatment with the M12MNCs, aging mice present enhanced motor ability and improved skeletal muscle metabolism. The results of in vivo and in vitro experiments confirm that M12MNCs reduce inflammation and decrease the expression of α-synuclein (α-syn). In addition, M12MNCs ameliorate skeletal muscle dysfunction in aging mice via regulating the SphK1/Spns2/S1PR2 axis. This study provides a therapeutic target of inflammatory and myogenic factors to improve the function of aging skeletal muscle, which provides valuable insights for the subsequent treatment of aging-related skeletal muscle function. These findings suggest that M12MNCs can improve age-related skeletal muscle dysfunction by modulating inflammation and cell proliferation, and can be used as a novel drug delivery system for clinical therapeutic regimens for muscle atrophy.