Neurological Emergency Treatment Strategy: A Neuron-Targeted Regulation System for Reactive Oxygen Species Metabolism through Ferroptosis Modulation
Yibo Ying, Xiong Cai, Peng Dai, Yuchao Zhang, Jiali Lv, Zhiyang Huang, Xuehai Chen, Yusi Hu, Yunjie Shi, Xiaokun Li, Dawei Jiang, Zhouguang Wang
Abstract
Spinal cord injury (SCI) represents a significant clinical challenge. Following SCI, the implementation of protective measures for neurons is critically important. Current clinical applications of hormone pulse therapy exhibit variable efficacy and considerable side effects, highlighting an urgent need for therapeutic strategies. This study investigates the pathological conditions of ischemia and hypoxia in the SCI region, complemented by early transcriptome sequencing postinjury. Our findings suggest that targeting ferroptosis is pivotal for early neuroprotection following SCI. Aiming at the cascade effect of mitochondrial damage leading to reactive oxygen species (ROS) production, along with extensive ROS-mediated lysosomal damage during ferroptosis signaling, we developed a liposome-based system for regulating iron metabolism─DTLS@CAT. This innovative liposome is designed to specifically target neuronal mitochondria, effectively eliminate mitoROS, and modulate complex interactions among iron metabolism, mitochondria, lysosomes, and ROS to facilitate recovery from SCI.