Feng Ruibing, Fan Yu, Zhang Xinya, Chen Lanmei, Zhong Zhang-Feng, Wang Yitao, Yu Hua, Zhang Qing-Wen, Li Guodong
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, P. R. China.
Macao Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, P. R. China.
ACS Nano. 2024 Jan 31;18(7):5951-64. doi: 10.1021/acsnano.4c00173.
Acute liver failure (ALF) is a rare and serious condition characterized by major hepatocyte death and liver dysfunction. Owing to the limited therapeutic options, this disease generally has a poor prognosis and a high mortality rate. When ALF cannot be reversed by medications, liver transplantation is often needed. However, transplant rejection and the shortage of donor organs still remain major challenges. Most recently, stem cell therapy has emerged as a promising alternative for the treatment of liver diseases. However, the limited cell delivery routes and poor stability of live cell products have greatly hindered the feasibility and therapeutic efficacy of stem cell therapy. Inspired by the functions of mesenchymal stem cells (MSCs) primarily through the secretion of several factors, we developed an MSC-inspired biomimetic multifunctional nanoframework (MBN) that encapsulates the growth-promoting factors secreted by MSCs via combination with hydrophilic or hydrophobic drugs. The red blood cell (RBC) membrane was coated with the MBN to enhance its immunological tolerance and prolong its circulation time in blood. Importantly, the MBN can respond to the oxidative microenvironment, where it accumulates and degrades to release the payload. In this work, two biomimetic nanoparticles, namely, rhein-encapsulated MBN (RMBN) and N-acetylcysteine (NAC)-encapsulated MBN (NMBN), were designed and synthesized. In lipopolysaccharide (LPS)/d-galactosamine (D-GalN)-induced and acetaminophen (APAP)-induced ALF mouse models, RMBN and NMBN could effectively target liver lesions, relieve the acute symptoms of ALF, and promote liver cell regeneration by virtue of their strong antioxidative, anti-inflammatory, and regenerative activities. This study demonstrated the feasibility of the use of an MSC-inspired biomimetic nanoframework for treating ALF.
急性肝衰竭（ALF）是一种罕见且严重的病症，其特征为大量肝细胞死亡和肝功能障碍。由于治疗选择有限，这种疾病通常预后较差且死亡率高。当药物无法逆转急性肝衰竭时，往往需要进行肝移植。然而，移植排斥和供体器官短缺仍然是主要挑战。最近，干细胞疗法已成为治疗肝脏疾病的一种有前景的替代方法。然而，有限的细胞递送途径和活细胞产品稳定性差极大地阻碍了干细胞疗法的可行性和治疗效果。受间充质干细胞（MSC）主要通过分泌多种因子发挥功能的启发，我们开发了一种受MSC启发的仿生多功能纳米框架（MBN），它通过与亲水性或疏水性药物结合来封装MSC分泌的促生长因子。红细胞（RBC）膜包裹在MBN上，以增强其免疫耐受性并延长其在血液中的循环时间。重要的是，MBN能够对氧化微环境做出反应，在其中积累并降解以释放所载药物。在这项工作中，设计并合成了两种仿生纳米颗粒，即大黄酸包裹的MBN（RMBN）和N-乙酰半胱氨酸（NAC）包裹的MBN（NMBN）。在脂多糖（LPS）/D-半乳糖胺（D-GalN）诱导和对乙酰氨基酚（APAP）诱导的急性肝衰竭小鼠模型中，RMBN和NMBN凭借其强大的抗氧化、抗炎和再生活性，能够有效靶向肝损伤部位，缓解急性肝衰竭的症状，并促进肝细胞再生。这项研究证明了使用受MSC启发的仿生纳米框架治疗急性肝衰竭的可行性。
