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Published on: August 7, 2020
Biohybrid hydrogel inhibiting β-klotho/HDAC3 axis for hepatocellular carcinoma treatment
Gaolin Wen1, Lingling Xue1, Mengdi Qiu1
1Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, China.
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 β-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.
Insights
A new biohybrid hydrogel targets β-klotho (KLB) to treat hepatocellular carcinoma (HCC). This hydrogel inhibits the FGF21-KLB pathway, effectively blocking HCC progression in vitro and in vivo.
Area of Science:
- Biomaterials Science
- Oncology
- Drug Delivery Systems
Background:
- Hepatocellular carcinoma (HCC) is a globally prevalent and highly invasive cancer with limited therapeutic options.
- Existing drug therapies for HCC often suffer from inadequate efficacy and poorly understood mechanisms of action.
- Targeting specific molecular pathways, such as the FGF21-KLB signaling pathway, presents a potential strategy for HCC treatment.
Purpose of the Study:
- To develop and evaluate a novel biohybrid hydrogel for targeted hepatocellular carcinoma (HCC) treatment.
- To investigate the efficacy of inhibiting the β-klotho (KLB) pathway using an HDAC3 inhibitor within a hydrogel system.
- To provide a promising anti-tumor drug delivery system for future clinical applications in HCC therapy.
Main Methods:
- Fabrication of a dual-network biohybrid hydrogel using gelatin methacryloyl (GelMA) and polyvinyl alcohol (PVA).
- Incorporation of the HDAC3 inhibitor RGFP966 into the hydrogel for controlled release and KLB inhibition.
- In vitro and in vivo validation of the hydrogel's efficacy in inhibiting HCC progression via the FGF21-KLB pathway.
Main Results:
- The GelMA/PVA hydrogel demonstrated excellent biocompatibility, storage stability, drug loading capacity, and water absorption.
- Selective inhibition of KLB activation by RGFP966 effectively blocked the FGF21-KLB signaling pathway.
- Significant inhibition of HCC progression was observed both in vitro and in vivo, confirming the hydrogel's anti-tumor potential.
Conclusions:
- The developed biohybrid hydrogel serves as an effective anti-tumor drug delivery system for hepatocellular carcinoma (HCC).
- Targeting the FGF21-KLB pathway with an HDAC3 inhibitor encapsulated in a hydrogel offers a promising therapeutic strategy.
- This innovative approach provides a strong theoretical foundation for advancing HCC treatment and future clinical translation.
