Reconstruction of TNF-α with specific isoelectric point released from SPIONs basing on variable charge to enhance pH-sensitive controlled-release.
Nanomedicine
; 60: 102758, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38852881
ABSTRACT
The clinical application of tumor necrosis factor-α (TNF-α) is limited by its short half-life, subeffective concentration in the targeted area and severe systemic toxicity. In this study, the recombinant polypeptide S4-TNF-α was constructed and coupled with chitosan-modified superparamagnetic iron oxide nanoparticles (S4-TNF-α-SPIONs) to achieve pH-sensitive controlled release and active tumor targeting activity. The isoelectric point (pI) of S4-TNF-α was reconstructed to approach the pH of the tumor microenvironment. The negative-charge S4-TNF-α was adsorbed to chitosan-modified superparamagnetic iron oxide nanoparticles (CS-SPIONs) with a positive charge through electrostatic adsorption at physiological pH. The acidic tumor microenvironment endowed S4-TNF-α with a zero charge, which accelerated S4-TNF-α release from CS-SPIONs. Our studies showed that S4-TNF-α-SPIONs displayed an ideal pH-sensitive controlled release capacity and improved antitumor effects. Our study presents a novel approach to enhance the pH-sensitive controlled-release of genetically engineered drugs by adjusting their pI to match the pH of the tumor microenvironment.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fator de Necrose Tumoral alfa
/
Preparações de Ação Retardada
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article