Minghao Li, Qiwei Yang, Jie Gao, Xudong Liu, Jihua Shi, Wenzhi Guo, Yi Zhang, Qiwen Yu, Xinzhi Sun, Shuijun Zhang
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引用次数: 0
Abstract
Background: Acute liver injury (ALI), a highly perilous clinical condition triggered by diverse etiological factors, frequently progresses to acute liver failure with life-threatening consequences. However, due to the limited intervention time window for ALF, donor shortages, challenges in utilizing marginal grafts, surgical complexity and risks, and the high economic burden, developing novel therapeutic strategies targeting ALI-induced ALF has become imperative. Methods: Through transcriptome analysis, we determined that ferroptosis is a key driver in the pathogenesis of ALI. To combat hepatocyte ferroptosis, we designed a novel mitochondria-targeted nanotuner (CPTD) for regulating mitochondrial oxidative stress and iron homeostasis imbalance during ALI. This nanotuner features a cerium oxide (CeO₂) nanozyme core with a polydopamine (PDA) coating, functionalized with triphenylphosphonium (TPP) for mitochondrial targeting and deferoxamine (DFO) for iron chelation. In vitro and in vivo experiments evaluated CPTD's ability to target mitochondria and the labile iron pool (LIP). Results: The nanotuner demonstrates dual regulatory capacity by effectively accumulating in hepatic mitochondria to concurrently scavenge reactive oxygen species (ROS) and sequester labile iron ions, thereby rectifying mitochondrial oxidative stress and iron dyshomeostasis. Comprehensive evaluations across multiple ALI models, mainly including hepatic ischemia-reperfusion injury and acetaminophen-induced hepatotoxicity, revealed that CPTD robustly inhibits ferroptosis, mitigates oxidative damage, attenuates inflammatory responses, and preserves hepatic function. Conclusions: Our findings establish this dual-targeting nanotuner as a promising therapeutic strategy for ALI, providing novel insights into mitochondrial redox and iron homeostasis modulation.
期刊介绍:
Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.