Lv Nan, Zhai Shaodong, Xiong Jun, Hu Nan, Guo Xiang, Liu Zhida, Zhang Ruiping
Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China.
Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, China; Shanxi Academy of Advanced Research and Innovation, Taiyuan 030032, China.
Colloids Surf B Biointerfaces. 2025 Jan;245:114193. doi: 10.1016/j.colsurfb.2024.114193. Epub 2024 Sep 2.
Pathological thrombus can cause serious acute diseases that present a significant threat to human health, such as myocardial infarction and stroke. Challenges remain in achieving effective thrombolysis and real-time monitoring of therapeutic effects while minimizing side effects. Herein,a multifunctional nanoplatform (TG-OPDEA@UK/MnO-H1080) with enhanced thrombus-permeability was developed to monitor the therapeutic effect of antioxidant-thrombolysis by hydroxyl radical-responsive NIR-II fluorescence imaging. The polyzwitterion poly (oxidized N,N-Diethylaminoethyl methacrylate-co-n-butyl methacrylate) (OPDEA) was prepared as the matrix of nanoparticles to simultaneously loading urokinase (UK) and MnO QDs, as well as NIR-II fluorescent molecule, H-1080. Subsequently, the fibrin targeted peptide CREKA was modified on the surface of the nanoparticles. OPDEA exhibits efficient loading capacity while endowing nanoparticles with the ability to effectively increased penetration depth of UK by 94.1 % into the thrombus, for extensive thrombolysis and fluorescence monitoring. The loaded UK exhibited good thrombolytic effect and greatly reduced the risk of bleeding by 82.6 %. TG-OPDEA@UK/MnO-H1080 showed good thrombolytic efficacy and specific thrombus monitoring in the mouse carotid artery thrombosis model induced by ferric chloride (FeCl). This work prepares a nanoplatform for thrombolytic therapy and real-time efficacy assessment based on an independent externally forced thrombus penetration delivery strategy.
病理性血栓可引发严重的急性疾病，对人类健康构成重大威胁，如心肌梗死和中风。在实现有效溶栓以及对治疗效果进行实时监测的同时将副作用降至最低方面，仍存在挑战。在此，我们开发了一种具有增强血栓渗透性的多功能纳米平台（TG-OPDEA@UK/MnO-H1080），通过羟基自由基响应近红外二区荧光成像来监测抗氧化溶栓的治疗效果。制备了聚两性离子聚（甲基丙烯酸N,N-二乙氨基乙酯-co-甲基丙烯酸正丁酯）（OPDEA）作为纳米颗粒的基质，用于同时负载尿激酶（UK）和MnO量子点以及近红外二区荧光分子H-1080。随后，在纳米颗粒表面修饰了纤维蛋白靶向肽CREKA。OPDEA展现出高效的负载能力，同时赋予纳米颗粒将UK有效渗透到血栓中的深度提高94.1%的能力，以实现广泛的溶栓和荧光监测。负载的UK表现出良好的溶栓效果，并将出血风险大幅降低了82.6%。在氯化铁（FeCl）诱导的小鼠颈动脉血栓形成模型中，TG-OPDEA@UK/MnO-H1080显示出良好的溶栓效果和特异性血栓监测能力。这项工作基于一种独立的外部强制血栓渗透递送策略，为溶栓治疗和实时疗效评估制备了一种纳米平台。
