Acylation of the antimicrobial peptide CAMEL for cancer gene therapy.
Drug Deliv
; 27(1): 964-973, 2020 Dec.
Article
en En
| MEDLINE
| ID: mdl-32611259
ABSTRACT
Obtaining ideal gene delivery vectors is still a major goal in cancer gene therapy. CAMEL, a short hybrid antimicrobial peptide, can kill cancer cells by membrane lysis. In this study, we constructed a series of non-viral vectors by attaching fatty acids with different chain lengths to the N-terminus of CAMEL. Our results showed that the cellular uptake and transfection efficiency of acyl-CAMEL started to significantly increase from a chain length of 12 carbons. C18-CAMEL was screened for gene delivery because it had the highest transfection efficiency. Surprisingly, C18-CAMEL/plasmid complexes displayed strong endosomal escape activity after entering cells via endocytosis. Importantly, C18-CAMEL could deliver p53 plasmids to cancer cells and significantly inhibited cell proliferation by the expression of p53. In addition, the C18-CAMEL/p53 plasmid complexes and the MDM2 inhibitor nutlin-3a showed significantly synergistic anticancer activity against MCF-7 cells expressing wild-type p53. Conclusively, our study demonstrated that conjugation of stearic acid to antimicrobial peptides is a simple and successful approach for constructing efficient and economical non-viral vectors for cancer gene therapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ácidos Esteáricos
/
Transfección
/
Proteínas Citotóxicas Formadoras de Poros
/
Vectores Genéticos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Drug Deliv
Asunto de la revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2020
Tipo del documento:
Article
País de afiliación:
China