Integrated Electrochemical Platform for Real-Time Monitoring of H₂O₂ Release and Alleviation of Cerebral Ischemia–Reperfusion Injury

Abstract To overcome the limited blood–brain barrier (BBB) permeability of the selective NLRP3 inhibitor OLT1177, a multifunctional nanoplatform named CS-CPTMS@CP1@OLT1177 was developed. This coordination polymer-based complex integrates targeted drug delivery with real-time electrochemical monitoring for the treatment of cerebral ischemia–reperfusion injury (CIRI). Constructed from chitosan (CS), compound 1, 3-(chloropropyl)trimethoxysilane (CPTMS), and the europium-based coordination polymer CP1, the final complex CS-CPTMS@CP1@OLT1177 exhibited excellent electrocatalytic activity toward H₂O₂ detection (0.1–100 μM, sensitivity 0.0124 μA/μM, detection limit 3.928 nM). In an oxygen-glucose deprivation/reoxygenation (OGD/R) microglial model, CS-CPTMS@CP1@OLT1177 significantly inhibited the release of pro-inflammatory cytokines IL-1β, IL-18, and TNF-α more effectively than free OLT1177. Molecular docking further supported the enhanced bioactivity of the Eu coordination framework, indicating potential synergistic therapeutic effects through hydrogen bonding interactions. This work establishes CS-CPTMS@CP1@OLT1177 as a promising platform for inflammation-targeted neuroprotection in ischemic stroke.