Cell membrane-camouflaged nanomedicines for enhanced thrombolysis and blood-brain barrier penetration in ischemic stroke therapy

Abstract

Thrombus-induced ischemic stroke (IS) remains a serious threat a serious health threat with limited therapeutic efficacy due to the dual challenges of precise thrombus targeting and restricted blood-brain barrier (BBB) penetration. While conventional nanocarriers, such as liposomes, micelles, and polymeric nanoparticles (NPs), demonstrate clinical potential due to their mature preparation protocols, their application is limited by poor targeting accuracy, inadequate biocompatibility, and rapid systemic clearance. In response, microenvironment-responsive biomimetic drug delivery systems based on cell membrane-camouflaged nanomedicines (CM-NMs) have emerged as a promising strategy, leveraging the pathological features of ischemic lesions for enhanced targeting and treatment. CM-NMs stand out by utilizing cell membranes to preserve innate targeting and/or BBB penetration capabilities. This approach also ensures high biocompatibility and minimizes the risk of immune clearance. This review highlights recent advances in CM-NMs for IS treatment, critically discussing three key approaches: (1) platelet membrane-camouflaged nanomedicines (PLM-NMs), which mimic platelet adhesion for thrombus-specific accumulation, (2) immune cell membrane NMs and stem cell membrane NMs, which leverage inflammatory tropism or homing mechanisms for enhanced BBB penetration, and (3) hybrid membrane NMs, which enable multi-targeting capabilities. Furthermore, we discuss ongoing challenges and clinical translation potential of CM-NMs to provide guidance for next-generation CM-NMs.