材料科学
肝衰竭
纳米技术
四面体
结晶学
组合化学
化学
生物
DNA
生物化学
内科学
医学
作者
Hongyan Wei,Ke Yi,Fenfang Li,Di Li,Jia-Zhen Yang,Run Shi,Yuanyuan Jin,Haixia Wang,Jianxun Ding,Yu Tao,Mingqiang Li
标识
DOI:10.1002/adma.202305826
摘要
Acute liver failure (ALF) is a life-threatening disease associated with the rapid development of inflammatory storms, reactive oxygen species (ROS) level elevation, and hepatocyte necrosis, which results in high short-term mortality. Except for liver transplantation, no effective strategies are available for ALF therapy due to the rapid disease progression and narrow therapeutic time window. Therefore, there is an urgent demand to explore fast and effective modalities for ALF treatment. Herein, a multifunctional tetrahedral DNA nanoplatform (TDN) is constructed by incorporating the tumor necrosis factor-α siRNA (siTNF-α) through DNA hybridization and antioxidant manganese porphyrin (MnP4) via π-π stacking interaction with G-quadruplex (G4) for surprisingly rapid and significant ALF therapy. TDN-siTNF-α/-G4-MnP4 silences TNF-α of macrophages by siTNF-α and polarizes them to the anti-inflammatory M2 phenotype, providing appropriate microenvironments for hepatocyte viability. Additionally, TDN-siTNF-α/-G4-MnP4 scavenges intracellular ROS by MnP4 and TDN, protecting hepatocytes from oxidative stress-associated cell death. Furthermore, TDN itself promotes hepatocyte proliferation via modulating the cell cycle. TDN-siTNF-α/-G4-MnP4 shows almost complete liver accumulation after intravenous injection and exhibits excellent therapeutic efficacy of ALF within 2 h. The multifunctional DNA nanoformulation provides an effective strategy for rapid ALF therapy, expanding its application for innovative treatments for liver diseases. This article is protected by copyright. All rights reserved.
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