Engineering CXCL12 Biomimetic Decoy-Integrated Versatile Immunosuppressive Nanoparticle for Ischemic Stroke Therapy with Management of Overactivated Brain Immune Microenvironment.
【作者】Shi, Jinjin; Yang, Yue; Yin, Na; Zhao, Yuzhen; Cheng, Hui; Zhou, Tonghai; Zhang,Zhenzhong; Zhang, Kaixiang
【期刊名】Small Methods
【影响因子】 2021年:14.188
【作者单位】School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China
【年，卷(期)：页码】2021, 2101158
【关键词】ischemic stroke;versatile immunosuppressive nanoparticle; biomimetic decoy; engineered mesenchymal stem cells; neurological repair
【摘要】Following ischemic stroke, brain-resident activated microglia and peripherally infiltrated inflammatory cells create complicated and overactivated brain immune microenvironment, which causes neuron death and dramatically hinders neurological functional recovery. Herein, we report an engineering CXCL12 biomimetic decoy-integrated versatile immunosuppressive nanoparticle (VIN) for management of overactivated brain immune microenvironment. The shell of VIN (membrane of CXCR4 overexpressed mesenchymal stem cells), can not only improve the homing of nanoparticles to the cerebral ischemic lesions, but also efficiently adsorb and neutralize CXCL12 to cut off infiltration of peripheral-neutrophils and mononuclear macrophages. The loaded A151 (cGAS inhibitor, telomerase repeat sequences) can inhibit cGAS-STING pathway in microglia, leading to microglia polarization toward an anti-inflammatory M2-like phenotype. Interestingly, A151 can be efficiently loaded onto the polydopaminenanospheres (PDA, the core of VIN) through the bridge of Zn2+. In the inflammatory site, PDA is oxidized by ROS, with the disappearance of Zn2+ complexation effect, and then A151 realizes a controlled release. In a model of rat ischemic stroke, VIN integrates inflammation tropism, peripherally inflammatory cells filtrate, brain-resident activated microglia polarization, as well as ROS scavenging, exerting outstanding therapeutic effects on ameliorating the mortality, reducing the infarct volume and protecting neurogenic functions of neurons.
【全文链接】
https://doi.org/10.1002/smtd.202101158
