Khalil Sara, Kanapathipillai Mathumai
Department of Mechanical Engineering, University of Michigan-Dearborn, Dearborn, MI 48128, USA.
Bioengineering (Basel). 2023 Jan 31;10(2):177. doi: 10.3390/bioengineering10020177.
Current tissue plasminogen-based therapeutic strategies for stroke suffer from systemic side effects and poor efficacy. Hence, novel drug delivery methods are needed to overcome these shortcomings. Exosome-based drug formulations have been shown to have superior therapeutic outcomes compared to conventional systemic drug delivery approaches. In this paper, we report exosome surface-coated tissue plasminogen activator (tPA)/catalase nanoformulations with improved thrombolytic efficacy compared to free tPA, which also reduce side effects. The results showed that the tPA exosome formulations retained tPA activity, improved tPA stability, exhibited significant fibrinolysis, and showed no significant toxicity effects. Further, when combined with antioxidant enzyme catalase, the formulation was able to inhibit hydrogen peroxide-mediated oxidative stress and toxicity. Hence, exosome-based tPA/catalase nanoformulations could have the potential to offer a safer and effective thrombolytic therapy.
目前基于组织纤溶酶原的中风治疗策略存在全身副作用和疗效不佳的问题。因此，需要新的药物递送方法来克服这些缺点。与传统的全身药物递送方法相比，基于外泌体的药物制剂已显示出更好的治疗效果。在本文中，我们报告了外泌体表面包被组织纤溶酶原激活剂（tPA）/过氧化氢酶的纳米制剂，与游离tPA相比，其溶栓效果有所改善，同时还能减少副作用。结果表明，tPA外泌体制剂保留了tPA活性，提高了tPA稳定性，表现出显著的纤维蛋白溶解作用，且未显示出明显的毒性作用。此外，当与抗氧化酶过氧化氢酶联合使用时，该制剂能够抑制过氧化氢介导的氧化应激和毒性。因此，基于外泌体的tPA/过氧化氢酶纳米制剂有可能提供一种更安全有效的溶栓治疗方法。
