Macropinocytosis-Inducible Extracellular Vesicles Modified with Antimicrobial Protein CAP18-Derived Cell-Penetrating Peptides for Efficient Intracellular Delivery.
Mol Pharm
; 18(9): 3290-3301, 2021 09 06.
Article
en En
| MEDLINE
| ID: mdl-34365796
ABSTRACT
The antimicrobial protein CAP18 (approximate molecular weight 18â¯000), which was first isolated from rabbit granulocytes, comprises a C-terminal fragment that has negatively charged lipopolysaccharide binding activity. In this study, we found that CAP18 (106-121)-derived (sC18)2 peptides have macropinocytosis-inducible biological functions. In addition, we found that these peptides are highly applicable for use as extracellular vesicle (exosomes, EV)-based intracellular delivery, which is expected to be a next-generation drug delivery carrier. Here, we demonstrate that dimerized (sC18)2 peptides can be easily introduced on EV membranes when modified with a hydrophobic moiety, and that they show high potential for enhanced cellular uptake of EVs. By glycosaminoglycan-dependent induction of macropinocytosis, cellular EV uptake in targeted cells was strongly increased by the peptide modification made to EVs, and intriguingly, our herein presented technique is efficiently applicable for the cytosolic delivery of the biologically cell-killing functional toxin protein, saporin, which was artificially encapsulated in the EVs by electroporation, suggesting a useful technique for EV-based intracellular delivery of biofunctional molecules.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sistemas de Liberación de Medicamentos
/
Péptidos Catiónicos Antimicrobianos
/
Exosomas
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Péptidos de Penetración Celular
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Saporinas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Pharm
Asunto de la revista:
BIOLOGIA MOLECULAR
/
FARMACIA
/
FARMACOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón