Although thrombolytic therapy has enjoyed relative success, limitations remain, such as a narrow therapeutic window and inconsistent efficacy. Consequently, there is a pressing need to develop novel therapeutic approaches. In recent years, extracellular vesicles (EVs) have garnered increasing attention as a potential alternative to stem cell therapy. Because of their ability to cross the blood–brain barrier and exert neuroprotective effects in cerebral ischemia and hemorrhage, the exploration of EVs for clinical application in stroke treatment is expanding. EVs are characterized by high heterogeneity, with their composition closely mirroring that of their parent cells. This property enables EVs to distinguish between cerebral ischemia and hemorrhage, thus facilitating a more rapid and accurate diagnosis. Additionally, EVs can be engineered to carry specific molecules, such as miRNAs, targeting them to specific cells, potentially enhancing the therapeutic outcome and improving stroke prognosis. In this review, we will also explore the methodologies for the isolation and extraction of EVs, critically evaluating the advantages and disadvantages of various commonly employed separation techniques. Furthermore, we will briefly address current EV preservation and administration methods, providing a comprehensive overview of the state of EV-based therapies in stroke treatment.

Intracerebral hemorrhage (ICH) carries a substantial global disease burden, and although it occurs less frequently than ischemic stroke, it results in a greater loss of disability-adjusted life years worldwide and is associated with one of the poorest prognoses among stroke patients. Due to the mechanisms of secondary injury following ICH, angiogenesis, inflammation, and oxidative stress (OS) levels in brain tissue are regulated by complex molecular pathways, leading to significant changes in the brain microenvironment (BME). While traditional treatments for ICH improve survival rates, they have notable drawbacks and limitations. Nanomedicines, as a promising approach, offer the potential to gradually overcome these limitations and are becoming increasingly important in ICH treatment research. This review provides an updated overview of the mechanisms behind the formation of the post-ICH BME, focusing on angiogenesis, inflammation, and OS. Conventional diagnostic and therapeutic methods are outlined, along with an analysis of their drawbacks and limitations. In addition, the current research status of nanomedicines targeting the post-ICH BME is systematically summarized from three perspectives: angiogenesis, inflammation, and OS. Finally, the progress of nanomedicines in clinical translation is analyzed, highlighting the challenges, opportunities, and future prospects for their application in the context of ICH.

Intracerebral hemorrhage (ICH) remains a life-threatening condition due to its high mortality and limited treatment options. This study explores a novel therapeutic strategy using engineered exosomes derived from endothelial progenitor cells (EPC-EXOs) to improve ICH outcomes. EPC-EXOs were modified with a CD47-enriched red blood cell membrane via co-extrusion to enhance their anti-phagocytic properties, thereby reducing degradation by activated microglia after ICH. A minimally invasive endoscopic-guided delivery system was developed to facilitate the targeted intranasal administration of these engineered EPC-EXOs (m-Oe-EXOs), allowing direct entry into brain tissue. We confirmed m-Oe-EXOs’ high retention and effective distribution in the brain. Functional analysis demonstrated that EPC-EXOs significantly promoted the proliferation, migration, and angiogenesis of brain microvascular endothelial cells (BMECs), with proteomic analysis identifying HSP90 as a key protein activating the Akt pathway in BMECs. In vivo, m-Oe-EXOs demonstrated therapeutic efficacy by improving blood-brain barrier integrity, reducing hematoma volume, and enhancing neurological recovery in ICH rats. Collectively, our findings highlight the potential of minimally invasive, endoscopic-guided delivery of m-Oe-EXOs as an innovative approach for ICH treatment, providing new insights into targeted, exosomes-based regenerative therapies.