Wan Mimi, Wang Qi, Wang Rongliang, Wu Rui, Li Ting, Fang Dan, Huang Yangyang, Yu Yueqi, Fang Leyi, Wang Xingwen, Zhang Yinghua, Miao Zhuoyue, Zhao Bo, Wang Fenghe, Mao Chun, Jiang Qing, Xu Xingquan, Shi Dongquan
National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China.
Jiangsu Province Key Laboratory of Environmental Engineering, School of Environment, Nanjing Normal University, Nanjing 210023, China.
Sci Adv. 2020 May 27;6(22):eaaz9014. doi: 10.1126/sciadv.aaz9014. eCollection 2020 May.
The treatment difficulties of venous thrombosis include short half-life, low utilization, and poor penetration of drugs at thrombus site. Here, we develop one kind of mesoporous/macroporous silica/platinum nanomotors with platelet membrane (PM) modification (MMNM/PM) for sequentially targeting delivery of thrombolytic and anticoagulant drugs for thrombus treatment. Regulated by the special proteins on PM, the nanomotors target the thrombus site and then PM can be ruptured under near-infrared (NIR) irradiation to achieve desirable sequential drug release, including rapid release of thrombolytic urokinase (3 hours) and slow release of anticoagulant heparin (>20 days). Meantime, the motion ability of nanomotors under NIR irradiation can effectively promote them to penetrate deeply in thrombus site to enhance retention ratio. The in vitro and in vivo evaluation results confirm that the synergistic effect of targeting ability from PM and motion ability from nanomotors can notably enhance the thrombolysis effect in both static/dynamic thrombus and rat model.
静脉血栓形成的治疗难点包括药物半衰期短、利用率低以及在血栓部位的渗透性差。在此，我们开发了一种具有血小板膜（PM）修饰的介孔/大孔二氧化硅/铂纳米马达（MMNM/PM），用于依次靶向递送溶栓和抗凝药物以治疗血栓。在PM上特殊蛋白质的调控下，纳米马达靶向血栓部位，然后PM可在近红外（NIR）照射下破裂，以实现理想的顺序药物释放，包括溶栓尿激酶的快速释放（3小时）和抗凝肝素的缓慢释放（>20天）。同时，纳米马达在NIR照射下的运动能力可有效促进它们深入渗透到血栓部位，以提高滞留率。体外和体内评估结果证实，PM的靶向能力与纳米马达的运动能力的协同作用可显著增强在静态/动态血栓和大鼠模型中的溶栓效果。
