Smart Delivery of Plasminogen Activators for Efficient Thrombolysis; Recent Trends and Future Perspectives

Fibrinolytic drugs have been successfully used to manage acute thrombotic and thromboembolic conditions. However, their narrow administration time window, rapid clearance, and possible inactivation limit their efficient and wider application. Most importantly, they present a substantial risk of fatal bleeding complications, which are a major cause of mortality and morbidity. Improving the therapeutic outcomes of pharmacological thrombolysis, including alleviating associated side effects, is an urgent challenge. In this context, nano-drug delivery systems have attracted major interest. State-of-the-art nanodelivery systems have achieved reduced immunogenicity and a significant prolongation of the biological half-life of drugs, the latter allowing their application as boli instead of infusions. Recent research focuses on theranostic systems capable of image-guided thrombolysis, clot targeting strategies, and stimuli-responsive systems. The latter are designed so that an external or internal stimulus triggers the drug release, offering unique spatiotemporal control over the treatment and potentially minimizing side effects. In this review, the authors discuss the different nanodelivery platforms and focus on stimuli-responsive systems, highlighting their therapeutic advantages and the challenges for their clinical translation.