National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, 210023, China.
Department of Vascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
J Mater Chem B. 2021 Oct 27;9(41):8659-8666. doi: 10.1039/d1tb01202a.
It is of great significance to find effective thrombolytic treatments due to the harm caused by thrombosis to human health. Based on the formation mechanism and complex microenvironment of a thrombus, polydopamine nanomotors (PDANMs) modified by the peptide of Arg-Gly-Asp (RGD) and loaded with urokinase (UK) were designed and prepared. A polydopamine (PDA) substrate has a good photothermal conversion effect. Under near-infrared (NIR) light irradiation, it can not only perform photothermal therapy (PTT) on thrombus, but also provide the driving force of PDANMs. Thrombolytic drug UK was loaded in the mesoporous structure of the PDA substrate and can be released at the thrombus site for drug therapy. The modified RGD can target the thrombus site, moreover, benefiting from the guanidine group of L-arginine in the peptide chain, and RGD can interact with reactive oxygen species (ROS) in the thrombus microenvironment to produce nitric oxide (NO). NO not only propelled the movement of nanomotors, but also promoted the growth of vascular endothelial cells to repair damaged blood vessels. The experimental results show that NIR and NO can provide dual driving sources for the nanosystem to achieve continuous and deep penetration of the drug-loaded nanomotors at the thrombus site, while realizing the photothermal and drug synergistic therapy to enhance the therapeutic effect and promote the growth of vascular endothelium cells. This kind of thrombus treatment strategy based on nanomotor drug delivery systems will provide good technical support for the clinical treatment of inferior vena cava thrombus.
找到有效的溶栓治疗方法具有重要意义，因为血栓对人类健康造成的危害极大。基于血栓的形成机制和复杂微环境，设计并制备了经精氨酸-甘氨酸-天冬氨酸（RGD）肽修饰、载尿激酶（UK）的聚多巴胺纳米马达（PDANMs）。聚多巴胺（PDA）基底具有良好的光热转换效果，在近红外（NIR）光照射下，不仅可以对血栓进行光热治疗（PTT），还可以为 PDANMs 提供驱动力。溶栓药物 UK 被装载在 PDA 基底的介孔结构中，并可在血栓部位释放以进行药物治疗。修饰后的 RGD 可以靶向血栓部位，此外，得益于肽链中 L-精氨酸的胍基，RGD 可以与血栓微环境中的活性氧（ROS）相互作用，产生一氧化氮（NO）。NO 不仅为纳米马达的运动提供了动力，还促进了血管内皮细胞的生长，从而修复受损的血管。实验结果表明，NIR 和 NO 可为纳米系统提供双重驱动力，使载药纳米马达在血栓部位持续、深入地渗透，同时实现光热和药物协同治疗，增强治疗效果，促进血管内皮细胞的生长。这种基于纳米马达药物递送系统的血栓治疗策略将为下腔静脉血栓的临床治疗提供良好的技术支持。
