TetrahedralFramework Nucleic Acid-Based DeliverySystem for miRNA-124 and Stroke-Homing Peptide: Targeted Therapy forAcute Ischemic Stroke

Acute ischemic stroke (AIS) is associated with a high mortality rate and poor prognosis, with a lack of effective therapeutic drugs for post-thrombolytic treatment. MicroRNA-based gene therapy is a promising approach for treating AIS, but its clinical application has been limited due to challenges, such as poor targeting efficiency, unsatisfactory stability, and inadequate cellular uptake. In this study, we successfully developed a microRNA-targeted delivery system based on the tetrahedral framework nucleic acid (tFNA). This nanodelivery system, guided by stroke-homing peptides, effectively targeted and delivered miRNA124 to the ischemic hemisphere. With the assistance of tFNA, miRNA124 efficiently entered cells and exerted therapeutic effects. Additionally, it promoted the transformation of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, reducing neuronal apoptosis and, ultimately, decreasing the infarct size and mortality rate. These findings present a promising therapeutic strategy for the targeted treatment of AIS.