Erythrocyte Membrane-Encapsulated SZF Nanocomposites for Hyperuricemia Therapy

Weiwei Liu¹Xin Guan²Luobing Wang¹Chengjie Zhang¹Boyi Shen¹Yuke Zeng¹Dongdong Li³Guangjin Pu⁴Jing Hu⁵Jiandong Gao^1*

• ¹Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
• ²Xiangshan Traditional Chinese Medicine Hospital, Huangpu District, Shanghai, China
• ³The Second Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
• ⁴Shanghai Fourth People's Hospital, Shanghai, China
• ⁵Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China

As a common disease, hyperuricemia is caused by metabolic disorders or excessive intake of purine-rich foods, leading to various health problems. Treatment efficacy is often hindered by poor patient compliance, significant side effects of pharmacotherapy, and the coexistence of multiple comorbidities. In this context, we have developed a red blood cell membrane-camouflaged Shizhifang nano-composite drug (SZF@PDA-RM), which can clear reactive oxygen species (ROS), inhibit inflammatory responses, maintain mitochondrial homeostasis, and reduce oxidative stress, thus effectively improving uric acid metabolism and kidney function. The nano-composite drug SZF@PDA-RM is formed by the co-polymerization of dopamine with the SZF formulation, which includes various traditional Chinese medicine components, and is further coated with a red blood cell membrane (RBC) to create a stable nano-composite drug. The RBC coating allows for prolonged circulation of the nano-drug in the bloodstream and reduces systemic toxicity. SZF@PDA-RM responds to elevated ROS levels in hyperuricemia, facilitating the sustained release of the SZF. The released SZF formulation negatively regulates uric acid-induced mitochondrial ROS production in renal tubular epithelial cells via the SHP2/ANT1 signaling pathway, inhibits the activation of the NLRP3 inflammasome, maintains mitochondrial homeostasis, and reduces oxidative stress. Tail vein injection of this nano-drug in hyperuricemia mice successfully improved uric acid metabolism and kidney function, thereby providing a novel paradigm for the safe and effective treatment of hyperuricemia.