The neuroinflammatory responses following ischemic stroke cause irreversible nerve cell death. Cell free-double strand DNA (dsDNA) segments from ischemic tissue debris are engulfed by microglia and sensed by their cyclic GMP-AMP synthase (cGAS), which triggers robust activation of the innate immune stimulator of interferon genes (STING) pathway and initiate the chronic inflammatory cascade. The decomposition of immunogenic dsDNA and inhibition of the innate immune STING are synergistic immunologic targets for ameliorating neuroinflammation. To combine the anti-inflammatory strategies of STING inhibition and dsDNA elimination, we constructed a DNase-mimetic artificial enzyme loaded with C-176. Nanoparticles are self-assembled by amphiphilic copolymers (P[CL₃₅-b-(OEGMA_20.7-co-NTAMA_14.3)]), C-176, and Ce⁴⁺ which is coordinated with nitrilotriacetic acid (NTA) group to form corresponding catalytic structures. Our work developed a new nano-drug that balances the cGAS-STING axis to enhance the therapeutic impact of stroke by combining the DNase-memetic Ce⁴⁺ enzyme and STING inhibitor synergistically. In conclusion, it is a novel approach to modulating central nervus system (CNS) inflammatory signaling pathways and improving stroke prognosis.

缺血性中风后的神经炎症反应导致不可逆的神经细胞死亡。来自缺血组织碎片的无细胞双链 DNA (dsDNA) 片段被小胶质细胞吞噬，并被其环 GMP-AMP 合酶 (cGAS) 感知，从而触发干扰素基因先天免疫刺激剂 (STING) 通路的强烈激活，并启动慢性炎症级联反应。免疫原性 dsDNA 的分解和先天免疫 STING 的抑制是改善神经炎症的协同免疫目标。为了结合 STING 抑制和 dsDNA 消除的抗炎策略，我们构建了一种负载 C-176 的 DNase 模拟人工酶。_{纳米粒子由两亲性共聚物(P[CL 35} - b -(OEGMA _20.7 - co -NTAMA _14.3 )])、C-176和Ce ⁴⁺自组装而成，与次氮基三乙酸(NTA)基团配位形成相应的催化催化剂结构。我们的工作开发了一种新的纳米药物，可平衡 cGAS-STING 轴，通过协同结合 DNase-memetic Ce 4+ 酶和^STING抑制剂来增强中风的治疗效果。总之，这是一种调节中枢神经系统（CNS）炎症信号通路和改善中风预后的新方法。