Development of a decellularized liver matrix-based nanomedicine for metabolic dysfunction-associated steatotic liver disease.

Abstract

The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) has increased, primarily because of excessive nutritional intake and sedentary lifestyles. However, clinical trials investigating therapeutic agents for this condition have reported them to have limited efficacy. In this study, we developed a novel nanomedicine comprising tannic acid (TA) and a decellularized liver matrix-TD-Nm-to promote recovery from MASLD. TD-Nm was synthesized and characterized, and in vitro (cellular model of oleic acid-induced fatty liver) and in vivo (two mouse models of MASLD) experiments were performed to evaluate its therapeutic efficacy. The in vitro experiments revealed that approximately 50% of the total TA was released from TD-Nm after 3 days. TD-Nm exhibited superior therapeutic efficacy to TA alone in the in vitro model, as evidenced by reduced lipid accumulation and lactate dehydrogenase activity as well as increased albumin and urea synthesis. The in vivo experiments revealed that TD-Nm reduced the liver-to-body weight ratio, intrahepatic lipid accumulation, and inflammation while enhancing hepatic function. In conclusion, this study introduced a promising novel therapeutic agent for MASLD, laying the foundation for future advancements in MASLD therapy.