COX-2靶向的近红外分子影像探针用于炎症和肿瘤的监测

环氧化酶-2（Cyclooxygenase-2，COX-2）是一种在炎症和肿瘤部位高表达的蛋白酶，因此能够用作分子影像学炎症和肿瘤监测的靶标.本文基于COX-2的小分子抑制剂（塞来昔布，Celecoxib）和水溶性近红外染料染料（ICG-Der-02，MPA）的COX-2靶向近红外探针（CMP），通过分子对接、动力学模拟和蛋白抑制实验验证了其对COX-2蛋白的结合能力.在细胞水平，CMP选择性积累在COX-2阳性细胞的细胞质中.动物炎症和肿瘤模型的荧光成像证实，CMP可以结合局部内源性COX-2并且表现出强烈的荧光.在此基础上，通过用塞来昔布预注射阻断COX-2活性位点可显着降低荧光，进一步证明了CMP的靶向特异性.因此，探针CMP具备优异的近红外光学成像能力和深层组织穿透，能够特异性地靶向COX-2高表达的炎症和肝癌移植瘤部位，具备炎症与肿瘤活体监测的应用前景.

COX-2 Targeted Near-Infrared Molecular Imaging Probe for Inflammation and Tumor Monitoring

Cyclooxygenase-2, which is a highly expressed protease in inflammation and tumor tissues, can serve as a monitor target for molecular imaging of inflammation and tumor. In this paper, a COX-2 targeted near-infrared probe (CMP) was synthesized based on a COX-2 small molecule inhibitor (celecoxib) and a water-soluble near-infrared dye (ICG-Der-02, MPA).The binding ability of COX-2 protein was verified by molecular docking, dynamic simulation and protein inhibition experiments. Results show that, at the cellular level, CMP can selectively accumulate at the cytoplasm of COX-2-positive cells. In vivo assays, probe guided-imaging in inflamed or cancerous tissues confirms that CMP can bind to the locally endogenic COX-2 and exhibit intense fluorescence. Importantly, the targeting specificity of CMP has been proved as the fluorescence can be significantly reduced by blocking COX-2 active site through preinjection with celecoxib. Therefore, the probe CMP, which possesses excellent near-infrared optical imaging capability and deep tissue penetration, and can specifically target to the high COX-2 site of inflammation and liver tumor, has the application prospect in inflammation and tumor monitoring.