In Situ Transformable Fibrillar networks Ameliorate Secondary Brain Injury after Intracerebral Hemorrhage by Activating KEAP1-Nrf2/ARE axis

Currently, there are no effective and long-lasting targeted treatments for secondary brain injury caused by ICH. Here, we report an in situ biomimetic self-assembly strategy based on a fibrillar, transformable peptide (NKF) that coordinately suppresses oxidative stress and neuroinflammation.

In aqueous solution, NKF self-assembles into nanoparticles; upon binding to KEAP1 in microglia, however, it undergoes an in situ transformation into nanofibrils, thereby enhancing intracellular retention and sustaining KEAP1 sequestration. In cellular and rat ICH models, NKF promotes sustained Nrf2 nuclear translocation and ARE-dependent transcription, resulting in enhanced antioxidant defense, attenuated pro-inflammatory signaling, and a shift in microglial phenotype towards a neuroprotective anti-inflammatory state.