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The treatment of ischemic stroke (IS) is seriously limited by insufficient drug accumulation in the ischemic lesions and ongoing secondary damage after ischemia-reperfusion. This paper reports a cRGD-functionalized exosome-based nanoplatform that can boost drug accumulation in ischemic lesions and enhance its antioxidant neuroprotective effects for IS therapy. We functionalized neural stem cell-derived exosomes with cyclic RGD peptides (cRGD) and then loaded Mn₃O₄ nanoparticles to create a hybrid nanosystem (cRGD-Exo@Mn₃O₄). The modified exosomes retained their inherent brain-targeting ability, while the cRGD modification promoted preferential accumulation in ischemic areas, likely through interaction with the highly expressed αvβ3 integrins in the ischemic lesions. The introduced Mn₃O₄ nanoparticles provided strong reactive oxygen species (ROS) scavenging capability, reducing oxidative stress in the ischemic microenvironment. Both in vitro and in vivo studies showed that cRGD-Exo@Mn₃O₄ accumulated more strongly in ischemic areas compared to unmodified controls. This nanosystem effectively alleviated oxidative stress and neuroinflammation, reducing infarct volume, easing brain edema, and improving neurological function in MCAO/R mice. Mechanistically, transcriptome analysis indicated that its therapeutic effects were linked to regulation of inflammation and cell death pathways, including inhibition of the RIPK1/RIPK3/MLKL signaling cascade. Overall, this study presents a rationally designed exosome-based nanoplatform that combines ischemic lesion-targeted accumulation with ROS scavenging capability.
We focus on custom functional materials in the field of nanomedicine. Based on your experimental needs, we can develop biofunctional nanomaterials, control material structure, particle size, and surface modification, and provide full characterization testing. The plan can be repeatedly optimized with full technical support throughout, supporting research projects in targeted delivery, bioimaging, nanodiagnostics, and therapy. Feel free to share your requirements, and we’ll evaluate customized solutions.
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