Therapeutic Effects of Self-Assembled Tetrahedral Framework Nucleic Acids on Liver Regeneration in Acute Liver Failure,ACS Applied Materials & Interfaces

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Therapeutic Effects of Self-Assembled Tetrahedral Framework Nucleic Acids on Liver Regeneration in Acute Liver Failure
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2022-03-14 , DOI: 10.1021/acsami.2c02523
Yang Chen _{1,

2,

3} , Sirong Shi ₄ , Bo Li _{1,

3} , Tian Lan ₅ , Kefei Yuan ₅ , Jingsheng Yuan _{1,

3} , Yongjie Zhou _{3,

6} , Jiulin Song _{1,

2,

3} , Tao Lv _{1,

2,

3} , Yujun Shi _{3,

6} , Bo Xiang ₂ , Taoran Tian ₄ , Tao Zhang ₄ , Jiayin Yang ₁ , Yunfeng Lin ₄

Affiliation

Liver failure is a serious disease that is characterized by global hepatocyte necrosis. Hepatocyte proliferation and liver regeneration are critically important for the success of treatments for liver disease. Tetrahedral framework nucleic acids (TFNAs), which are widely used antioxidants and anti-inflammatory nanomaterials, activate multiple proliferation and prosurvival pathways. Therefore, the effects of a TFNA on hepatocyte proliferation and liver regeneration in mouse livers injured by 70% partial hepatectomy (PHx), acetaminophen overdose, and carbon tetrachloride were explored in this study. The TFNA, which was successfully self-assembled from four specifically designed ssDNAs, entered the body quickly and was taken up effectively by hepatocytes in the liver and could eventually be cleared by the kidneys. The TFNA promoted hepatocyte proliferation in vitro by activating the Notch and Wnt signaling pathways. In the three in vivo mouse models of liver injury, the TFNA attenuated the injuries and enhanced liver regeneration by regulating the cell cycle and the P53 signaling pathway. Therefore, by promoting hepatocyte proliferation and enhancing liver regeneration, the TFNA shows potential as an effective therapeutic agent for treating acute liver injury induced by 70% PHx and other factors, thereby preventing the progression to acute liver failure and reducing the associated mortality rate.

中文翻译：

自组装四面体骨架核酸对急性肝功能衰竭肝再生的治疗作用

肝功能衰竭是一种严重的疾病，其特征是全球肝细胞坏死。肝细胞增殖和肝再生对于肝病治疗的成功至关重要。四面体骨架核酸 (TFNA) 是广泛使用的抗氧化剂和抗炎纳米材料，可激活多种增殖和促生存途径。因此，本研究探讨了 TFNA 对 70% 部分肝切除术 (PHx)、对乙酰氨基酚过量和四氯化碳损伤的小鼠肝脏中肝细胞增殖和肝再生的影响。由四个专门设计的 ssDNA 成功自组装而成的 TFNA 迅速进入体内，并被肝脏中的肝细胞有效吸收，最终可被肾脏清除。TFNA 通过激活 Notch 和 Wnt 信号通路在体外促进肝细胞增殖。在肝损伤的三种体内小鼠模型中，TFNA 通过调节细胞周期和 P53 信号通路来减轻损伤并增强肝再生。因此，通过促进肝细胞增殖和增强肝再生，TFNA显示出作为治疗由70% PHx和其他因素引起的急性肝损伤的有效治疗剂的潜力，从而防止进展为急性肝衰竭并降低相关死亡率。

更新日期：2022-03-14

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