Journal
JOURNAL OF CONTROLLED RELEASE
Volume 353, Issue -, Pages 675-684Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2022.12.026
Keywords
Click chemistry; Exosomes; Multiple sclerosis; Resveratrol; Sialic acid
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A synthetic sialic acid analogue was successfully used for exosome labeling, leading to the development of a resveratrol-loaded exosome formulation for multiple sclerosis treatment. The study demonstrated the feasibility and efficacy of engineered exosome administration as a potential therapeutic strategy for CNS diseases.
Despite exosome promise as endogenous drug delivery vehicles, the current understanding of exosome may be insufficient to develop their various applications. Here we synthesized five sialic acid analogues with different length N-acyl side chains and screened out the optimal metabolic precursor for exosome labeling via bio-orthogonal click chemistry. In proof-of-principle labeling experiments, exosomes derived from macrophages (RAW-Exo) strongly co-localized with central nervous system (CNS) microglia. Inspired by this discovery, we developed a resveratrol-loaded RAW-Exo formulation (RSV&Exo) for multiple sclerosis (MS) treatment. Intra-nasal administration of RSV&Exo significantly inhibited inflammatory responses in the CNS and peripheral system in a mouse model of MS and effectively improved the clinical evolution of MS in vivo. These findings suggested the feasibility and efficacy of engineered RSV&Exo administration for MS, providing a potential therapeutic strategy for CNS diseases.
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