A cathepsin B/GSH dual-responsive fluorinated peptide for effective siRNA delivery to cancer cells.
Bioorg Chem
; 135: 106485, 2023 06.
Article
em En
| MEDLINE
| ID: mdl-36963370
ABSTRACT
Small interfering RNA (siRNA) can be exploited to silence specific genes associated with cancer development, and successful siRNA therapy is highly dependent on the efficiency of the siRNA delivery vector. Herein, a well-designed novel redox- and enzyme-responsive fluorinated polyarginine (PFC-PR) was developed to be used as an anti-cancer siRNA carrier. The multiple guanidine groups could provide positive charges and bind with siRNA efficiently, and further fluorination modification enhanced the interaction with siRNA, resulting in a more stable PFC-PR/siRNA nanocomplex, improving serum tolerance, and promoting cellular uptake and endosome escape. Meanwhile, the PFC-PR was responsive to overexpressed cathepsin B and high levels of glutathione in cancer cells, conferring its ability to enhance siRNA release within cancer cells and making it cancer-targeting. Consequently, PFC-PR showed good biocompatibility and high gene silencing efficiency, which could inhibit cancer cell growth when delivered the siRNA targeting vascular endothelial growth factor, suggesting that it can be potentially used for anti-cancer gene therapy applications.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator A de Crescimento do Endotélio Vascular
/
Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China