靶向小胶质细胞亚型的甘露糖-金团簇荧光纳米探针的构建及其活体成像研究

As an important immune cell of the central nervous system, microglia has "double-edged sword" function of induction and inhibition of the inflammatory response after the central nervous system injury. However the physiological and pathological functions of microglia in the central nervous system injury are still controversial, which is partially due to its sensitivity to the external environment. Hence it is urgent to develop new in vivo imaging probes to further clarity microglia's fuctions with low interference and highly sensitive..On the basis of brain tissue engineering from the applicant and noble metal cluster fluorescent nanoprobes from the research group, fluorescent nanoprobe with NIR excitation/emission and high-penetrability will be synthesized from gold cluster as fluorophore and mannose as both stabilizers and targeting molecules. Further assay in chemical systems and cell culture system will be used to study the stability and targeting of the probe. The cytotoxicity will also be studied. Lastly the probe was utilized for in vivo imaging in the mouce model of acute inflammation in lateral ventricle to obtain the distribution and migration images of mannose receptor-positive microglia subtypes..These results provide direct evidences to clarify the role of mannose receptor-positive microglia subtypes in the central nervous system injury and regeneration. Combined with the results of immunohistochemical staining and in vitro assay, the physiological and pathological function of microglia would be further confirmed, which promote the progress of the central nervous system injury and regeneration study.

小胶质细胞作为中枢神经系统（CNS）的重要免疫细胞，在CNS损伤后具有诱导和抑制炎症反应的"双刃剑"功能。但由于小胶质细胞对外界环境较为敏感，现阶段对其在CNS损伤中的作用仍不明确，亟需低干扰、高敏感的活体标记方法进一步明确其功能。.本项目基于申请人在脑损伤再生及所在课题组在贵金属团簇荧光纳米探针领域的研究基础，制备具有近红外激发/发射光谱、较强血脑屏障穿透能力的甘露糖-金团簇荧光纳米探针；进一步在化学体系和细胞培养体系下分别研究探针的稳定性和靶向性，并考察其细胞毒性；最后选择在脑损伤再生中起重要作用的甘露糖受体（MR）阳性小胶质细胞亚型作为靶细胞，利用该探针在小鼠急性侧脑室炎症模型中进行活体成像，得到细胞的体内分布及迁移图像。.这些活体成像结果为阐明MR阳性小胶质细胞亚型在CNS损伤再生中的作用提供了直接证据，进一步明确小胶质细胞的复杂生理、病理功能，推动CNS损伤再生研究发展。

本项目基于前期在贵金属团簇荧光纳米探针领域的研究基础，制备具有优异荧光特性的纳米探针；进一步在化学体系和细胞培养体系下分别研究探针的稳定性和靶向性，并考察其细胞毒性；初步研究了探针的生物标记和成像效果。