Yuan Ying, Diao Shanchao, Zhang Dong, Yi Wanrong, Qi Baiwen, Hu Xiang, Xie Chen, Fan Quli, Yu Aixi
Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
State Key Laboratory of Organic Electronics and Information Displays, and Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing, 210023, China.
Mater Today Bio. 2023 Jun 9;21:100697. doi: 10.1016/j.mtbio.2023.100697. eCollection 2023 Aug.
Anastomotic thrombosis prevalently causes anastomosis failure, accompanied with ischemia and necrosis, the early diagnosis of which is restricted by inherent shortcomings of traditional imaging techniques in clinic and lack of appropriate prodromal biomarkers for thrombosis initiation. Herein, a fresh thrombus-specific molecular event, protein disulfide isomerase (PDI) is innovatively chosen as the activating factor, and a thrombosis targeting and PDI-responsive turn-on near infrared II (NIR-II) fluorescence nanoprobe is firstly developed. The supramolecular complex-based nanoprobe IR806-PDA@BSA-CREKA is fabricated by assembling NIR-II emitting cyanine derivative IR806-PDA with bovine serum albumin (BSA), which could ameliorate the stability and pharmacokinetics of the nanoprobe, addressing the contradiction in the balance of brightness and biocompatibility. The NIR-II-off nanoprobe exhibits robust turn-on NIR-II fluorescence upon PDI-specific activation, and . Of note, the constructed nanoprobe demonstrates superior photophysical stability, efficient fibrin targeting peptide-derived thrombosis binding and a maximum signal-to-background ratio (SBR) of 9.30 for anastomotic thrombosis in NIR-II fluorescent imaging In conclusion, the exploited strategy enables positive visualized diagnosis for anastomotic thrombosis and dynamic monitoring for thrombolysis of fresh fibrinolytic thrombus, potentially contributes a novel strategy for guiding the therapeutic selection between thrombolysis and thrombectomy for thrombosis treatment in clinic.
吻合口血栓形成普遍会导致吻合口失败,并伴有缺血和坏死,其早期诊断受到临床传统成像技术固有缺点的限制,且缺乏用于血栓形成起始的合适前驱生物标志物。在此,创新性地选择了一种新鲜血栓特异性分子事件——蛋白二硫键异构酶(PDI)作为激活因子,并首次开发了一种靶向血栓形成且对PDI有响应的近红外二区(NIR-II)荧光纳米探针。基于超分子复合物的纳米探针IR806-PDA@BSA-CREKA是通过将发射NIR-II的花菁衍生物IR806-PDA与牛血清白蛋白(BSA)组装而成,这可以改善纳米探针的稳定性和药代动力学,解决了亮度和生物相容性平衡方面的矛盾。该NIR-II关闭型纳米探针在PDI特异性激活后表现出强烈的开启NIR-II荧光。值得注意的是,构建的纳米探针在NIR-II荧光成像中显示出优异的光物理稳定性、高效的纤维蛋白靶向肽衍生的血栓结合能力以及吻合口血栓形成时9.30的最大信噪比(SBR)。总之,所开发的策略能够对吻合口血栓形成进行阳性可视化诊断,并对新鲜纤维蛋白溶解血栓的溶栓过程进行动态监测,可能为临床血栓形成治疗中指导溶栓和血栓切除术之间的治疗选择贡献一种新策略。