Targeting Early Apoptosis in Acute Ischemic Stroke with a Small-Molecule Probe
Cheng Qian, Dong-Fang Liu, Cong-Xiao Wang, Jie Ding, Yan-Li An, Pei-Cheng Li, Gao-Jun Teng
文献索引：10.1021/acsbiomaterials.8b00213
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摘要
Inhibiting apoptotic cells helps ameliorate ischemic injury. Actually, only the apoptotic cells in early stage could be rescued. Molecular imaging of the early apoptosis would make sense in ischemic stroke; however, few of apoptosis molecular probes could specifically target early apoptosis. This study developed a small-molecule early apoptosis targeting probe CYS-F, which was synthesized by cystine with fluorescein isothiocyanate dyes. And the final molecular weight of CYS-F was only 1013 Da, which was much smaller than the traditional apoptosis marker annexin V. CYS-F showed excellent early apoptosis targeting ability both in vitro and in vivo. And CYS-F was cleared rapidly from the circulation with a blood half-life of 1.325 h. A favorable match was obtained between the images in fluorescence imaging and magnetic resonance imaging in stroke models. The target-to-background ratio of the lesions on 0 h was negative, which reflected the decreased blood flow. Multimodal molecular imaging showed the therapeutic effect of cystamine was dose dependence and CYS-F could also predict the outcome of ischemic stroke at an early stage. The versatility of CYS-F provides a comprehensive and convenient route for clinical decision-making in acute ischemic stroke.