Versatile functionalization of Bifidobacteria-derived extracellular vesicles using amino acid metabolic labeling and click chemistry for immunotherapy.
Int J Pharm
; 661: 124410, 2024 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-38954931
ABSTRACT
Extracellular vesicles (EVs) are nanoparticles secreted by various organisms. Methods for modifying EVs functionally have garnered attention for developing EV-based therapeutic systems. However, most technologies used to integrate these functions are limited to mammalian-derived EVs and a promising modification method for bacteria-derived EVs has not yet been developed. In this study, we propose a novel method for the versatile functionalization of immunostimulatory probiotic Bifidobacteria-derived EVs (B-EVs) using amino acid metabolic labeling and azide-alkyne click reaction. Azide D-alanine (ADA), a similar molecule to D-alanine in bacteria cell-wall peptidoglycan, was selected as an azide group-functionalized amino acid. Azide-modified B-EVs were isolated from Bifidobacteria incubated with ADA. The physicochemical and compositional characteristics, as well as adjuvanticity of B-EVs against immune cells were not affected by azide loading, demonstrating that this functionalization approach can retain the endogenous usefulness of B-EVs. By using the fluorescent B-EVs obtained by this method, the intracellular trafficking of B-EVs after uptake by immune cells was successfully observed. Furthermore, this method enabled the formulation of B-EVs for hydrogelation and enhanced adjuvanticity in the host. Our findings will be helpful for further development of EV-based immunotherapy.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Azidas
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Bifidobacterium
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Química Click
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Vesículas Extracelulares
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Imunoterapia
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article