Biohybrid hydrogel inhibiting ß-klotho/HDAC3 axis for hepatocellular carcinoma treatment.
Int J Biol Macromol
; 277(Pt 3): 134369, 2024 Oct.
Article
in En
| MEDLINE
| ID: mdl-39098678
ABSTRACT
Hepatocellular carcinoma (HCC), ranking as the fourth most prevalent cancer globally, has garnered significant attention due to its high invasiveness and mortality rates. However, drug therapies face challenges of inadequate efficacy and unclear mechanisms. Here, we propose a novel biohybrid hydrogel that targets ß-klotho (KLB) for HCC treatment. As a dual-network hydrogel, this gel combines gelatin methacryloyl (GelMA) and polyvinyl alcohol (PVA) to ensure biocompatibility while enhancing controlled drug release. Notably, it exhibits good storage stability, high drug load capacity, and efficient water absorption. By introducing the HDAC3 inhibitor RGFP966, we can selectively inhibit the activation of KLB. This deactivation effectively blocks the FGF21-KLB signaling pathway and inhibits the progression of HCC. Importantly, we have successfully validated this unique phenomenon both in vivo and in vitro, providing substantial evidence for the efficacy of this hydrogel-based anti-tumor drug delivery system as a promising strategy for HCC treatment. This innovative research outcome brings new hope to the field of tumor therapy, providing a reliable theoretical foundation for future clinical applications.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Hepatocellular
/
Hydrogels
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Klotho Proteins
/
Histone Deacetylases
/
Liver Neoplasms
Limits:
Animals
/
Humans
Language:
En
Journal:
Int J Biol Macromol
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Netherlands