Microenvironmental Control of MUC1 Aptamer-Guided Acid-Labile Nanoconjugate within Injectable Microporous Hydrogels.
Bioconjug Chem
; 28(10): 2530-2537, 2017 10 18.
Article
em En
| MEDLINE
| ID: mdl-28949511
ABSTRACT
Although aptamers are well-known as cell-specific membrane biomarkers for tumor-targeted therapy, it is important to avoid their degradation by nucleases in vivo. In this study, we developed a MUC1 aptamer-doxorubicin nanoconjugate (APT-DOX) through an acid-labile linkage and embedded APT-DOX into a thermosensitive hydrogel for antitumor therapy. The hydrogels exhibit a sol-gel transition upon intratumoral injection, resulting in the protection and controlled release control of APT-DOX with the shielding of the gel network. Moreover, the released APT-DOX was prone to be enriched at the tumor cells due to specific intracellular transport by the overexpressing MUC1 protein; however, APT-DOX regained the free DOX form via the rupture of the linkage under tumor cells lysosome acidic conditions and achieved increased concentration in the nucleus for antitumor treatment.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Portadores de Fármacos
/
Mucina-1
/
Hidrogéis
/
Aptâmeros de Nucleotídeos
/
Nanoconjugados
/
Microambiente Tumoral
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article