Su Yina, Huang Linjie, Xu Guizhen, Chen Simin, Wu Jiaqiong, Wang Siyu, Zhang Yichao, Lin Xiahui
School of Medical Imaging, Fujian Medical University, Fuzhou, Fujian, 350122, P. R. China.
Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, P. R. China.
Adv Healthc Mater. 2025 May;14(12):e2404960. doi: 10.1002/adhm.202404960. Epub 2025 Mar 24.
Traditional antithrombotic therapeutic strategies encounter challenges including heightened bleeding risks, short circulation times, low targeting ability, and inferior thrombus penetration. Therefore, a novel thrombolysis nanodrug (APBUL) is designed that incorporates urokinase (UK) loaded onto the surface of bowl-shaped nanomotors (APBs) encapsulated within fibrin peptide (CREKA)-modified thermosensitive liposomes, presenting an innovative therapeutic platform for thrombolysis. APBUL leverages CREKA's targeting ability for thrombus accumulation. Subsequently, under the irradiation of near-infrared light, the thermosensitive liposomal shell undergoes controlled disruption, releasing internal APBs and UK. Then, the APBs move directionally though thermophoresis effect, facilitating photothermal therapy and deep thrombus penetration, and synergistically enhancing UK release and diffusion to optimize thrombolysis. Moreover, the APBUL possesses a catalase-like activity, catalyzing hydrogen peroxide into oxygen to alleviate oxidative stress and inflammatory factors at the thrombus site, thereby lowering the recurrence risk. Combined with the ability of APBUL's photoacoustic imaging, this new strategy is expected to provide an inspiring idea for the integrated use of clinical thrombolytic therapy in diagnosis, imaging, and treatment.
传统的抗血栓治疗策略面临诸多挑战，包括出血风险增加、循环时间短、靶向能力低以及血栓穿透性差等问题。因此，设计了一种新型溶栓纳米药物（APBUL），它将负载有尿激酶（UK）的碗状纳米马达（APBs）包裹在纤维蛋白肽（CREKA）修饰的热敏脂质体内，为溶栓提供了一个创新的治疗平台。APBUL利用CREKA对血栓的靶向积累能力。随后，在近红外光照射下，热敏脂质体外壳受到可控破坏，释放出内部的APBs和UK。然后，APBs通过热泳效应定向移动，促进光热治疗和深入血栓穿透，并协同增强UK的释放和扩散，以优化溶栓效果。此外，APBUL具有类似过氧化氢酶的活性，可将过氧化氢催化分解为氧气，减轻血栓部位的氧化应激和炎症因子，从而降低复发风险。结合APBUL的光声成像能力，这一新策略有望为临床溶栓治疗在诊断、成像和治疗中的综合应用提供一个具有启发性的思路。
