Fan Yongliang, Liu Li, Li Fang, Zhou Hang, Ye Yizhou, Yuan Chunping, Shan Hongli, Zang Wangfu, Luo Yu, Yan Sijing
Department of Cardio-Thoracic Surgery, Shanghai 10th People's Hospital, School of Clinical Medicine of Nanjing Medical University, Shanghai, China.
Department of Cardiovascular Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Bioeng Biotechnol. 2022 Aug 9;10:923365. doi: 10.3389/fbioe.2022.923365. eCollection 2022.
Urokinase is widely used in the dissolution of an acute pulmonary embolism due to its high biocatalytic effect. However, how to precisely regulate its dose, avoid the side effects of hemolysis or ineffective thrombolysis caused by too high or too low a dose, and seize the golden time of acute pulmonary embolism are the key factors for its clinical promotion. Therefore, based on the precise design of a molecular structure, an ultrasonic-responsive nanoliposome capsule was prepared in this paper. Singlet oxygen is continuously generated under the interaction of the ultrasonic cavitation effect and the sonosensitizer protoporphyrin, and the generated singlet oxygen will break the thiol acetone bond between the hydrophilic head and the hydrophobic tail of the liposome, and the lipid The body structure disintegrates rapidly, and the urokinase encapsulated inside is rapidly released, down-regulating the expression of fibrinogen in the body, and exerting a thrombolytic function. The and results show that the smart urokinase nanoliposomes prepared by us have sensitive and responsive cytocompatibility to ultrasound and good thrombolytic properties for acute pulmonary embolism, which provides a new strategy for clinical acute pulmonary embolism thrombolysis.
由于具有高生物催化作用,尿激酶被广泛用于急性肺栓塞的溶栓治疗。然而,如何精确调节其剂量,避免因剂量过高或过低导致溶血或溶栓无效等副作用,以及抓住急性肺栓塞的黄金治疗时间,是其临床推广的关键因素。因此,本文基于分子结构的精确设计,制备了一种超声响应纳米脂质体胶囊。在超声空化效应与声敏剂原卟啉的相互作用下持续产生单线态氧,所产生的单线态氧会破坏脂质体亲水头部与疏水尾部之间的硫醇丙酮键,脂质体结构迅速解体,包裹在内部的尿激酶快速释放,下调体内纤维蛋白原的表达,发挥溶栓功能。 和 结果表明,我们制备的智能尿激酶纳米脂质体对超声具有敏感且响应性的细胞相容性,对急性肺栓塞具有良好的 溶栓性能,为临床急性肺栓塞溶栓提供了新策略。