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Engineered Brain-Targeted Exosomes Delivering FGF1 for Sustained Glycemic Regulation and Multitarget Neurovascular Protection in Diabetic Stroke
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DOI：10.1002/advs.77064.png)
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Abstract
En 中文
Diabetic stroke is characterized by a hyperglycemic and pro-inflammatory microenvironment that exacerbates neurovascular dysfunction. However, the blood–brain barrier (BBB) remains a formidable obstacle, restricting the delivery of most therapeutic molecules. To address this, we developed a non-invasive treatment strategy using engineered exosomes. Specifically, we fabricated FGF1-loaded exosomes functionalized with the rabies virus glycoprotein (RVG) peptide (FGF1-RVG Exo). This platform facilitates selective, neuron-targeted delivery of FGF1 to the ischemic penumbra via RVG-mediated transcytosis. In a diabetic stroke mouse model, FGF1-RVG Exo exhibited superior pharmacological efficacy compared to free FGF1, achieving robust therapeutic outcomes with only once-weekly administration. Notably, a single dose during the acute phase elicited a sustained hypoglycemic effect lasting up to two weeks and effectively ameliorated systemic insulin resistance. Locally, the accumulation of exosomes within the lesion led to a significant reduction in infarct volume and cell apoptosis, while promoting neovascularization and the recovery of motor and cognitive functions. This brain-targeted strategy achieves a peripheral–central synergistic modulation, addressing the multi-target requirements of diabetic stroke management. Collectively, our findings provide a novel paradigm for treating diabetic ischemic stroke and a potent strategy for the targeted delivery of growth factors to the central nervous system.
Keywords:
brain targeted drug delivery system
fibroblast growth factor
ischemic stroke
neural targeting
type 2 diabetes
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