Tang Chunming, Wang Qianqian, Li Kaiming, Li Xiuqi, Wang Cong, Xue Lingjing, Ju Caoyun, Zhang Can
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing, P.R. China.
Biomater Sci. 2021 Aug 7;9(15):5247-5258. doi: 10.1039/d1bm00566a. Epub 2021 Jun 17.
Neuroinflammation plays a key role in the progression of brain injury induced by stroke, and has become a promising target for therapeutic intervention for stroke. Monitoring this pivotal process of neuroinflammation is highly desirable to guide specific therapy. However, there is still a lack of a satisfactory nanoprobe to selectively monitor neuroinflammation. As endothelial cell activation is a hallmark of neuroinflammation, it would be clinically relevant to develop a non-invasive in vivo imaging technique to detect the endothelial activation process. Herein, inspired by the specific neutrophil-endothelium interaction, we designed neutrophil-camouflaged magnetic nanoprobes (NMNPs) that can be used to target activated endothelial cells for improved neuroinflammation imaging. NMNPs are composed of an inner core of superparamagnetic iron oxide (SPIO)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles and a biomimetic outer shell of a neutrophil membrane, which maintained the biocompatibility and targeting ability of neutrophils and the excellent contrast effects of SPIO. Moreover, we demonstrated that NMNPs can successfully bind to inflamed cerebral vasculature using the intravital imaging of live cerebral microvessels in transient middle cerebral artery occlusion (tMCAO) mice. After that, NMNPs could further accumulate in the brain vasculature and exhibit excellent contrast effects for stroke-induced neuroinflammation and biosafety. We believe that the neutrophil-camouflaged magnetic nanoprobe could serve as a highly safe and selective nanoprobe for neuroinflammation imaging and has alluring prospects for clinical application.
神经炎症在中风诱导的脑损伤进展中起关键作用，并已成为中风治疗干预的一个有前景的靶点。监测这一关键的神经炎症过程对于指导特异性治疗非常必要。然而，仍然缺乏一种令人满意的纳米探针来选择性地监测神经炎症。由于内皮细胞活化是神经炎症的一个标志，开发一种非侵入性的体内成像技术来检测内皮活化过程具有临床相关性。在此，受中性粒细胞与内皮细胞特异性相互作用的启发，我们设计了中性粒细胞伪装的磁性纳米探针（NMNPs），可用于靶向活化的内皮细胞以改善神经炎症成像。NMNPs由负载超顺磁性氧化铁（SPIO）的聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒内核和中性粒细胞膜仿生外壳组成，其保持了中性粒细胞的生物相容性和靶向能力以及SPIO的优异对比效果。此外，我们通过对短暂性大脑中动脉闭塞（tMCAO）小鼠活体脑微血管的活体成像证明，NMNPs能够成功结合到炎症性脑血管。之后，NMNPs可进一步在脑血管中蓄积，并对中风诱导的神经炎症表现出优异的对比效果和生物安全性。我们相信，中性粒细胞伪装的磁性纳米探针可作为一种高度安全且选择性的神经炎症成像纳米探针，具有诱人的临床应用前景。
