A Novel Near-Infrared Fluorescence Imaging Probe for in Vivo Neutrophil Tracking
A Novel Near-Infrared Fluorescence Imaging Probe for in Vivo Neutrophil Tracking
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DOI：
10.2310/7290.2011.00054
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发表时间：
2012-09
影响因子：
2.8
通讯作者：
Li Xiao;Yi Zhang;S. Berr;M. Chordia;P. Pramoonjago;L. Pu;D. Pan
中科院分区：
文献类型：
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作者：
Li Xiao;Yi Zhang;S. Berr;M. Chordia;P. Pramoonjago;L. Pu;D. Pan
利用小鼠耳部炎症模型，研制并验证了一种多镜近红外荧光探针，肉桂酰基-F-(D)L-F-(D)L-F-聚乙二醇-花青素7(cFlF-PEG-Cy7)，靶向中性粒细胞上的甲酰肽受体。在给药前24小时，左耳局部应用佛波醇-12-肉豆蔻酸酯-13-醋酸酯诱发小鼠急性炎症。在探针注射后24小时内进行无创的NIRF成像。该探针的体内中性粒细胞靶向性通过预先给药过量的非荧光肽cFlFlF-PEG的阻断研究和扰乱的肽探针cLFFFL-PEG-Cy7的成像研究来表征。注射肉桂酰-L-F-L-聚乙二醇-花青素7的小鼠的近红外荧光成像显示，在注射后24小时，炎症的左耳的荧光强度大约是对照右耳的4倍。相比之下，在注射后24小时，扰乱探针和阻断研究获得的比率分别是1.5倍和2倍。此外，一项显微免疫组织学研究证实，cFlF-PEG-Cy7的NIRF信号与炎症组织中激活的中性粒细胞有关。有了这个探针，体内中性粒细胞的趋化作用可以在活体动物中进行相关的宏观成像，并在组织和细胞水平上进行微观成像。
The development and validation of a multiscopic near-infrared fluorescence (NIRF) probe, cinnamoyl-F-(D)L-F-(D)L-F-PEG-cyanine7 (cFlFlF-PEG-Cy7), that targets formyl peptide receptor on neutrophils using a mice ear inflammation model is described. Acute inflammation was induced in mice by topical application of phorbol-12-myristate-13-acetate to left ears 24 hours before probe administration. Noninvasive NIRF imaging was longitudinally performed up to 24 hours following probe injection. The in vivo neutrophil-targeting specificity of the probe was characterized by a blocking study with preadministration of excess nonfluorescent peptide cFlFlF-PEG and by an imaging study with a scrambled peptide probe cLFFFL-PEG-Cy7. NIRF imaging of mice injected with cinnamoyl-L-F-F-F-L-PEG-cyanine7 (cFlFlF-PEG-Cy7) revealed that the fluorescence intensity for inflamed left ears was approximately fourfold higher than that of control right ears at 24 hours postinjection. In comparison, the ratios acquired with the scrambled probe and from the blocking study were 1.5- and 2-fold at 24 hours postinjection, respectively. Moreover, a microscopic immunohistologic study confirmed that the NIRF signal of cFlFlF-PEG-Cy7 was associated with activated neutrophils in the inflammatory tissue. With this probe, in vivo neutrophil chemotaxis could be correlatively imaged macroscopically in live animals and microscopically at tissue and cellular levels.