Ischemic strokes: exploring the challenges of translating nanomedicine into clinical practice

Acute ischemic strokes (AIS) represent a major health concern with more than 12 million deaths per year. Despite the establishment of intravenous thrombolysis as the main line of treatment three decades ago, and the subsequent advent of endovascular therapy, most patients remain disabled. While nanomedicine has shown considerable promise in the management of strokes over the years, there remains a gap between the numerous preclinical studies and the paucity of related clinical trials. In the last five years, around 250 articles described preclinical nanomedicine-based approaches to tackle AIS. These articles explore multiple directions to alleviate AIS, including firstly neuroprotection, followed by the use of thrombolysis through various approaches. Notably, they show a broad variety in the in vivo model choice as well as key readouts, making comparison across protocols difficult. Moreover, relevant data for clinical translation is often lacking, such as biodistribution and organ toxicity, pharmacokinetics, or stability of the proposed nanomaterials. On the other hand, only a few clinical trials have involved nanoparticles, with mixed results. Thus, it can be proposed that among the obstacles hindering the clinical application of the often-promising nanomaterials, the major challenges are the insufficient characterization of nanomaterials including storage, stability, biodistribution, toxicity, and pharmacokinetics; diversity of in vivo protocols, hyper-focused ischemia–reperfusion damages compared to thrombolysis; and a necessity to acknowledge the complexity of AIS thrombi when designing a therapeutic approach. However, ongoing research considering the speed and feasibility requirements for AIS might result in future improvement in patient care.