A Neutrophil Hijacking Nanoplatform Reprograming NETosis for Targeted Microglia Polarizing Mediated Ischemic Stroke Treatment

• DOI: 10.1002/advs.202305877
• Publication Date: 2024-03-06T07:45:55Z
• Authors: Na Yin; Wenya Wang; Fei Pei; Yuzhen Zhao; Changhua Liu; Mingming Guo; Kaixiang Zhang; Zhenzhong Zhang; Jinjin Shi; Yun Zhang; Zhi‐Hao Wang; Junjie Liu
• Keywords: Neutrophil Extracellular Traps; Stroke

Precise and efficient regulation of microglia is vital for ischemic stroke therapy prognosis. The infiltration neutrophils into the brain provides opportunities regulatory drugs across blood-brain barrier, while hindered by neutrophil extracellular traps (NETs) targeted delivery intracerebral to microglia. This study reports an hijacking nanoplatform (referred as APTS) A151 (a telomerase repeat sequence) without generation NETs. In middle cerebral artery occlusion (MCAO) mouse model, efficiency tissues increases fourfold. APTS dramatically reduces formation NETs 2.2-fold via reprogramming NETosis apoptosis in a reactive oxygen species scavenging-mediated citrullinated histone 3 inhibition pathway. Noteworthy, within repackaged apoptotic bodies following death pattern reprogramming, which, when engulfed microglia, polarizes anti-inflammatory M2 phenotype. After four times treatment, infarction area group decreases 5.1-fold. Thus, feasible, efficient, practical drug approach reshaping immune microenvironment treating disorders central nervous system.