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

Index: 10.1021/acsbiomaterials.8b00213

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Abstract

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.