Biomimetic propofol liposomes alleviate ischemic stroke by targeting ferroptosis via EGFR/Nrf2 pathway activation

作者：Guibo Fan, A. Hongyu Zhang, Ayang Zhao, Yueyue Gao, Yuting Rong, Rui Xin, Liangcan He, Sihua Qi · 发表于：Materials & Design · 年份：2026 · DOI：10.1016/j.matdes.2026.115627 · 被引用次数：3 · 研究领域：Ferroptosis and cancer prognosis、Neuroinflammation and Neurodegeneration Mechanisms、Immune cells in cancer

• A macrophage membrane–camouflaged, stimulus-responsive nanocarrier enables precise and efficient delivery of propofol to ischemic brain regions. • Targeted propofol delivery overcomes major translational barriers, including limited brain accumulation, rapid drug clearance, and poor retention at ischemic lesions. • This work demonstrates that propofol confers neuroprotection by inhibiting ferroptosis via activation of the EGFR/NRF2 signaling pathway, thereby restoring mitochondrial homeostasis and improving neurological outcomes. Ischemic stroke remains a leading cause of death and long-term disability worldwide, with therapeutic efficacy limited by narrow treatment windows and severe ischemia–reperfusion injury. Excessive oxidative stress and neuroinflammation drive progressive neuronal injury after ischemia–reperfusion, with ferroptosis emerging as a key downstream form of regulated cell death, thereby underscoring the need for lesion-specific and sustained neuroprotective interventions. Propofol exhibits intrinsic antioxidant, mitochondrial-protective, and anti-ferroptotic activities beyond its anesthetic effects. However, its therapeutic application in ischemic stroke is constrained by insufficient accumulation at ischemic lesion sites and rapid systemic clearance, resulting in unstable neuroprotective efficacy. In this study, we developed a macrophage membrane–coated lipid nanoparticle loaded with propofol (MCM@LNP@Propofol), integrating efficient liposomal encapsulatio...