PDF(Pubmed)
Abstract：
Liver fibrosis could be the last hope for treating liver cancer and remodeling of the hepatic microenvironment has emerged as a strategy to promote the ablation of liver fibrosis. In recent years, especially with the rapid development of nanomedicine, hepatic microenvironment therapy has been widely researched in studies concerning liver cancer and fibrosis. In this comprehensive review, we summarized recent advances in nano therapy-based remodeling of the hepatic microenvironment. Firstly, we discussed novel strategies for regulatory immune suppression caused by capillarization of liver sinusoidal endothelial cells (LSECs) and macrophage polarization. Furthermore, metabolic reprogramming and extracellular matrix (ECM) deposition are caused by the activation of hepatic stellate cells (HSCs). In addition, recent advances in ROS, hypoxia, and impaired vascular remodeling in the hepatic fibrotic microenvironment due to ECM deposition have also been summarized. Finally, emerging nanotherapeutic approaches based on correlated signals were discussed in this review. We have proposed novel strategies such as engineered nanotherapeutics targeting antigen-presenting cells (APCs) or direct targeting T cells in liver fibrotic immunotherapy to be used in preventing liver fibrosis. In summary, this comprehensive review illustrated the opportunities in drug targeting and nanomedicine, and the current challenges to be addressed.
摘要：
肝纤维化可能是治疗肝癌的最后希望，肝微环境的重塑已成为促进肝纤维化消融的策略。近年来,特别是随着纳米医学的快速发展，肝微环境治疗在肝癌和纤维化的研究中得到了广泛的研究。在这次全面审查中，我们总结了基于纳米疗法的肝微环境重塑的最新进展。首先,我们讨论了由肝窦内皮细胞（LSEC）毛细血管化和巨噬细胞极化引起的调节性免疫抑制的新策略。此外，代谢重编程和细胞外基质（ECM）沉积是由肝星状细胞（HSC）的激活引起的。此外,ROS的最新进展，缺氧,还总结了由于ECM沉积导致的肝纤维化微环境中血管重塑受损。最后,这篇综述讨论了基于相关信号的新兴纳米治疗方法。我们已经提出了新的策略，如工程纳米治疗靶向抗原呈递细胞（APC）或直接靶向T细胞在肝纤维化免疫疗法中用于预防肝纤维化。总之,这篇全面的综述说明了药物靶向和纳米医学的机遇，以及当前需要解决的挑战。
