Guanidyl and imidazolyl integration group-modified PAMAM for gastric adenocarcinoma gene therapy.
J Gene Med
; 22(10): e3240, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-32558063
ABSTRACT
BACKGROUND:
Gene therapy has become a potential strategy for cancer treatment. However, the development of efficient gene vectors restricts the application for cancer gene treatment. Functionalization of polymers with functional groups can significantly improve their transfection efficacy.METHODS:
Guanidyl can form bidentate hydrogen with the phosphate groups and phosphate groups are present in DNA and cell membranes, thus increasing DNA condensation and cellular uptake. Imidazolyl has high buffering capacity in endosomal/lysosomal acidic environment, facilitating endosome/lysosome escape. We designed a structure-integrated group of guanidyl and imidazolyl, 2-aminoimidazole (AM), which was conjugated to PAMAM generation 2 (G2) for gene therapy of gastric adenocarcinoma.RESULTS:
Molecular docking results illustrated that G2-AM bound with DNA molecule effectively via multiple interactions. A quantitative luciferase assay showed that the transfection efficacy of G2-AM/pGL3 was approximately 100-fold greater than that of G2/pGL3, 90-fold greater than that of imidazolyl-modified G2 (G2-M) /pGL3 and 100-fold greater than that of G5/pGL3 without additional cytotoxicity. After introducing the pTRAIL gene into gastric adenocarcinoma cells, the apoptosis ratio of gastric adenocarcinoma cells treated with G2-AM/pTRAIL was 36.95%, which is much larger than the corresponding ratio of G2/pTRAIL (7.45%), G2-M/pTRAIL (11.33%) and G5/pTRAIL (23.2%). In a gastric adenocarcinoma xenograft model, the in vivo transfection efficacy of G2-AM/pRFP was much greater than that of G2/pRFP and G2-M/pRFP.CONCLUSIONS:
These results demonstrate that AM could be modified with cationic polymers for potential application in gene delivery and gastric adenocarcinoma gene therapy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
/
Terapia Genética
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Adenocarcinoma
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Dendrímeros
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Gene Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China