Pathogenesis-adaptive polydopamine nanosystem for sequential therapy of ischemic stroke.
Pathogenesis-adaptive polydopamine nanosystem for sequential therapy of ischemic stroke.
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用于缺血性卒中序贯治疗的病机适应性多巴胺纳米系统。
DOI：
10.1038/s41467-023-43070-z
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发表时间：
2023-11-06
影响因子：
16.6
通讯作者：
Chen, Zhong
中科院分区：
文献类型：
--
作者：
Wu, Di;Zhou, Jing;Zheng, Yanrong;Zheng, Yuyi;Zhang, Qi;Zhou, Zhuchen;Chen, Xiaojie;Chen, Qi;Ruan, Yeping;Wang, Yi;Chen, Zhong
缺血性脑卒中是一种致死性脑血管疾病，再灌注作为主要的血供恢复策略可引起严重的缺血性脑损伤。再灌注后的神经炎症是脑卒中药物治疗的主要障碍，其动态进展使精准治疗成为一项艰巨的任务。在这项工作中，我们报道了一种用于缺血性卒中序次治疗的发病适应性多多巴胺纳米系统。纳米系统的内在自由基清除能力和定制的介观结构可以在初始阶段减弱氧化应激。在后期小胶质细胞过度激活时，二甲胺四环素负载纳米系统可以及时逆转促炎转变，以响应激活的基质金属蛋白酶-2，提供按需调节。进一步的脑卒中体内研究表明，与单一治疗和联合治疗相比，序贯策略具有更高的存活率和更好的脑恢复。补充令人满意的生物安全性结果，这种用于脑卒中后神经炎症的顺序和按需调节的自适应纳米系统是缺血性脑卒中治疗的一种很有前途的方法。再灌注是缺血性脑卒中后恢复血液供应的主要策略，但其引起的神经炎症是动态进展的，阻碍了缺血性脑卒中的治疗。在这里，作者报告了一种致病适应性纳米系统，用于缺血性卒中治疗中再灌注诱导的动态神经炎症的顺序和按需调节。
Ischemic stroke is lethal cerebrovascular disease, and reperfusion as the main strategy of blood supply restoration can cause severe ischemic brain damage. Considered as the major obstacle in medication for stroke, neuroinflammation after reperfusion undergoes dynamic progression, making precision treatment for stroke a Herculean task. In this work, we report a pathogenesis-adaptive polydopamine nanosystem for sequential therapy of ischemic stroke. Intrinsic free radical scavenging and tailored mesostructure of the nanosystem can attenuate oxidative stress at the initial stage. Upon microglial overactivation at the later stage, minocycline-loaded nanosystem can timely reverse the pro-inflammatory transition in response to activated matrix metalloproteinase-2, providing on-demand regulation. Further in vivo stroke study demonstrates a higher survival rate and improved brain recovery of the sequential strategy, compared with mono-therapy and combined therapy. Complemented with satisfactory biosafety results, this adaptive nanosystem for sequential and on-demand regulation of post-stroke neuroinflammation is a promising approach to ischemic stroke therapy. Reperfusion is a main strategy for restoring blood supply after ischemic stroke, but it induces neuroinflammation that undergoes dynamic progression, hindering the treatment of ischemic stroke. Here, the authors report a pathogenesis-adaptive nanosystem for sequential and on-demand regulation of reperfusion-induced dynamic neuroinflammation for ischemic stroke therapy.
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DOI：
10.1002/advs.202101526
发表时间：
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期刊：
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影响因子：
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