Engineered Brain‐Targeted Exosomes Delivering FGF1 for Sustained Glycemic Regulation and Multitarget Neurovascular Protection in Diabetic Stroke
- 1State Key Laboratory of Macromolecular Drugs and Large‐scale Preparation School of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang China
- 2Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health) School of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang China
Abstract
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.
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BibTeX
@article{shen2026engineered,
title = {{Engineered Brain‐Targeted Exosomes Delivering FGF1 for Sustained Glycemic Regulation and Multitarget Neurovascular Protection in Diabetic Stroke}},
author = {Bixin Shen and Chengxiang Zhang and Junhui Wang and Xichong Zhong and Shihao Chen and Xue Wang and Xiaokun Li and Li Lin},
journal = {Advanced Science},
year = {2026},
month = aug,
doi = {10.1002/advs.77064},
url = {https://doi.org/10.1002/advs.77064},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Engineered Brain‐Targeted Exosomes Delivering FGF1 for Sustained Glycemic Regulation and Multitarget Neurovascular Protection in Diabetic Stroke
AU - Bixin Shen
AU - Chengxiang Zhang
AU - Junhui Wang
AU - Xichong Zhong
AU - Shihao Chen
AU - Xue Wang
AU - Xiaokun Li
AU - Li Lin
PY - 2026
DA - 2026/08/11
JO - Advanced Science
DO - 10.1002/advs.77064
UR - https://doi.org/10.1002/advs.77064
AB - 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.
SN - 2198-3844
ER -