Comparative Proteomics Inspired Self-Stimulated Release Hydrogel Reinforces the Therapeutic Effects of MSC-EVs on Alzheimer's Disease.

Autor: Huang M; Department of Pharmacology and Chemical Biology, Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China., Zheng M; Department of Pharmacology and Chemical Biology, Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China., Song Q; Department of Pharmacology and Chemical Biology, Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China., Ma X; Department of Pharmacology and Chemical Biology, Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China., Zhang Q; Department of Pharmacology and Chemical Biology, Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China., Chen H; Department of Pharmacology and Chemical Biology, Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China., Jiang G; Department of Pharmacology and Chemical Biology, Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China., Zhou S; Department of Pharmacy, Shanghai Pudong Hospital, Fudan University, 2800 Gongwei Road, Shanghai, 201399, China., Chen H; Institute of Interdisciplinary Integrative Biomedical Research, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China., Wang G; Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China., Dai C; Daxing Research Institute, University of Science and Technology Beijing, Beijing, 102600, China., Li S; Cellular Biomedicine Group Inc, Shanghai, 201210, China., Li P; Cellular Biomedicine Group Inc, Shanghai, 201210, China., Wang H; Department of Pharmacology and Chemical Biology, Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China., Zhang A; School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, 200240, China., Huang Y; Department of Pharmacology and Chemical Biology, Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China., Chen J; Department of Pharmacy, Shanghai Pudong Hospital, Fudan University, 2800 Gongwei Road, Shanghai, 201399, China., Gao X; Department of Pharmacology and Chemical Biology, Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Jazyk: angličtina
Zdroj: Advanced materials (Deerfield Beach, Fla.) [Adv Mater] 2024 Apr; Vol. 36 (14), pp. e2311420. Date of Electronic Publication: 2023 Dec 29.
DOI: 10.1002/adma.202311420
Abstrakt: The clinical application of extracellular vesicles (EVs)-based therapeutics continues to be challenging due to their rapid clearance, restricted retention, and low yields. Although hydrogel possesses the ability to impede physiological clearance and increase regional retention, it typically fails to effectively release the incorporated EVs, resulting in reduced accessibility and bioavailability. Here an intelligent hydrogel in which the release of EVs is regulated by the proteins on the EVs membrane is proposed. By utilizing the EVs membrane enzyme to facilitate hydrogel degradation, sustained retention and self-stimulated EVs release can be achieved at the administration site. To achieve this goal, the membrane proteins with matrix degrading activity in the mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are identified using comparative proteomics. After that, a hydrogel comprised of self-assembled peptides that are susceptible to degradation by the membrane enzymes present in MSC-EVs is designed and synthesized. After intranasal administration, this peptide hydrogel facilitates sustained and thermo-sensitive release of MSC-EVs, thereby extending the retention of the MSC-EVs and substantially enhancing their potential for treating Alzheimer's disease. This research presents a comparative proteomics-driven approach to intelligent hydrogel design, which holds the capacity to significantly enhance the applicability of EVs in clinical settings.
(© 2023 Wiley‐VCH GmbH.)
Databáze: MEDLINE
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