Macrophage-Disguised Manganese Dioxide Nanoparticles for Neuroprotection by Reducing Oxidative Stress and Modulating Inflammatory Microenvironment in Acute Ischemic Stroke.
Macrophage-Disguised Manganese Dioxide Nanoparticles for Neuroprotection by Reducing Oxidative Stress and Modulating Inflammatory Microenvironment in Acute Ischemic Stroke.
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巨噬细胞——伪装的二氧化锰纳米颗粒通过减少氧化应激和调节急性缺血性中风的炎症微环境来保护神经
DOI：
10.1002/advs.202101526
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Jiang C
中科院分区：
文献类型：
--
作者：
Li C;Zhao Z;Luo Y;Ning T;Liu P;Chen Q;Chu Y;Guo Q;Zhang Y;Zhou W;Chen H;Zhou Z;Wang Y;Su B;You H;Zhang T;Li X;Song H;Li C;Sun T;Jiang C
再灌注损伤仍然是阻碍缺血性脑卒中神经元存活的主要挑战。然而，目前的临床治疗仍然停留在单一的病理过程上，这是由于缺乏全面的神经保护作用。本研究开发了一种巨噬细胞伪装的蜂窝状二氧化锰（MnO2）纳米球，负载fingolimod （FTY）来挽救缺血半暗区。特别是，仿生纳米颗粒可以通过巨噬细胞膜蛋白介导的识别，在受损的血管内皮上过度表达细胞粘附分子，在受损的大脑中积极积累。MnO2纳米球可以消耗过量的过氧化氢（H2O2）并将其转化为所需的氧气（O2），并在酸性溶酶体中分解释放货物，从而减少氧化应激，促进M1型小胶质细胞向M2型转变，最终逆转促炎微环境，增强受损神经元的存活。这种仿生纳米药物为缺血性脑卒中的多靶点联合治疗提供了新的策略。巨噬细胞伪装的满载MnO2纳米颗粒（Ma@(MnO2+FTY)）被设计用于挽救缺血半暗区。纳米颗粒可以通过消耗活性氧和产生氧气，在缺血区域积极积累，直接保护神经元。此外，纳米颗粒还可以通过多种信号通路促进小胶质细胞的表型转变，从而逆转促炎微环境，增加对受损神经元的保护作用。
Reperfusion injury is still a major challenge that impedes neuronal survival in ischemic stroke. However, the current clinical treatments are remained on single pathological process, which are due to lack of comprehensive neuroprotective effects. Herein, a macrophage‐disguised honeycomb manganese dioxide (MnO2) nanosphere loaded with fingolimod (FTY) is developed to salvage the ischemic penumbra. In particular, the biomimetic nanoparticles can accumulate actively in the damaged brain via macrophage‐membrane protein‐mediated recognition with cell adhesion molecules that are overexpressed on the damaged vascular endothelium. MnO2 nanosphere can consume excess hydrogen peroxide (H2O2) and convert it into desiderated oxygen (O2), and can be decomposed in acidic lysosome for cargo release, so as to reduce oxidative stress and promote the transition of M1 microglia to M2 type, eventually reversing the proinflammatory microenvironment and reinforcing the survival of damaged neuron. This biomimetic nanomedicine raises new strategy for multitargeted combined treatment of ischemic stroke. Macrophage‐disguised FTY‐loaded MnO2 nanoparticles (Ma@(MnO2+FTY)) are engineered to salvage the ischemic penumbra. Nanoparticles can accumulate actively in the ischemic region to protect neurons directly via consuming ROS and generating O2. In addition, the nanoparticles can also reverse the proinflammatory microenvironment by promoting the phenotypic transition of microglia through multiple signaling pathways, increasing the protection effects on damaged neurons.
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DOI：
10.1177/0271678x15606723
发表时间：
2016-02
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
Østergaard L;Engedal TS;Moreton F;Hansen MB;Wardlaw JM;Dalkara T;Markus HS;Muir KW
通讯作者：
Muir KW
影响因子：
8.3
作者：
Kawaguchi, Akira T.;Fukumoto, Dai;Tsukada, Hideo
通讯作者：
Tsukada, Hideo
微血栓——针对急性缺血性中风的神经血管重塑和增强微循环灌注的胶束
影响因子：
29.4
作者：
Lu, Yifei;Li, Chao;Jiang, Chen
通讯作者：
Jiang, Chen
影响因子：
8.3
作者：
Gelderblom, Mathias;Leypoldt, Frank;Magnus, Tim
通讯作者：
Magnus, Tim
影响因子：
4.2
作者：
Bowen, Kellie K.;Naylor, Michelle;Vemuganti, Raghu
通讯作者：
Vemuganti, Raghu