From liver fibrosis to hepatocarcinogenesis: Role of excessive liver H(2)O(2) and targeting nanotherapeutics.
From liver fibrosis to hepatocarcinogenesis: Role of excessive liver H(2)O(2) and targeting nanotherapeutics.
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DOI：
10.1016/j.bioactmat.2022.11.001
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发表时间：
2023-05
影响因子：
18.9
通讯作者：
Cao, Gang
中科院分区：
文献类型：
--
作者：
Shao, Meiyu;Wang, Yifan;Dong, Hongyan;Wang, Lu;Zhang, Xiaoqing;Han, Xin;Sang, Xianan;Bao, Yini;Peng, Mengyun;Cao, Gang
肝纤维化和肝细胞癌（HCC）是当今世界性的威胁。肝纤维化在早期是可逆的，但在晚期会发展为肝癌前病变。在病理性肝脏中，过量的H2O2产生并积累，这影响肝细胞、枯否细胞（KCs）和肝星状细胞（HSC）的功能，导致纤维化和HCC的发生。H2O2的积累与超氧阴离子（O2·−）的过量产生和抗氧化酶系统的破坏有关。许多以H2O2为靶点的治疗药物以不同的方式对肝纤维化或HCC显示出令人满意的效果。本文就H2O2在肝组织中蓄积的原因、H2O2在肝纤维化和肝癌发生中的作用作一综述。此外，针对H2O2的纳米治疗药物进行了总结，以进一步考虑抗纤维化或抗肿瘤治疗。肝纤维化和肝癌密切相关，因为ROS引起的肝损伤和炎症，特别是过度积累的H2O2。病理肝脏中过量的H2O2扩散是由于代谢率增加和细胞抗氧化系统减少。自由扩散的H2O2损伤肝脏特异性细胞，从而导致纤维化和肝癌发生。本文综述了以H2O2为靶点的纳米药物在肝纤维化和肝癌治疗中的应用，并提出了目前面临的挑战。
Liver fibrosis and hepatocellular carcinoma (HCC) have been worldwide threats nowadays. Liver fibrosis is reversible in early stages but will develop precancerosis of HCC in cirrhotic stage. In pathological liver, excessive H2O2 is generated and accumulated, which impacts the functionality of hepatocytes, Kupffer cells (KCs) and hepatic stellate cells (HSCs), leading to genesis of fibrosis and HCC. H2O2 accumulation is associated with overproduction of superoxide anion (O2•−) and abolished antioxidant enzyme systems. Plenty of therapeutics focused on H2O2 have shown satisfactory effects against liver fibrosis or HCC in different ways. This review summarized the reasons of liver H2O2 accumulation, and the role of H2O2 in genesis of liver fibrosis and HCC. Additionally, nanotherapeutics targeting H2O2 were summarized for further consideration of antifibrotic or antitumor therapy. Liver fibrosis and HCC are closely related because ROS induced liver damage and inflammation, especially over-cumulated H2O2. Excess H2O2 diffusion in pathological liver was due to increased metabolic rate and diminished cellular antioxidant systems. Freely diffused H2O2 damaged liver-specific cells, thereby leading to fibrogenesis and hepatocarcinogenesis. Nanotherapeutics targeting H2O2 are summarized for treatment of liver fibrosis and HCC, and also challenges are proposed.
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