Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, China.
Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, China.
Int J Biol Macromol. 2024 Oct;277(Pt 3):134369. doi: 10.1016/j.ijbiomac.2024.134369. Epub 2024 Aug 2.
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.
肝细胞癌（HCC）是全球第四大常见癌症，由于其高侵袭性和高死亡率而备受关注。然而，药物治疗面临疗效不足和机制不明确的挑战。在这里，我们提出了一种针对 HCC 治疗的新型生物杂交水凝胶，该水凝胶靶向β-klotho（KLB）。作为一种双网络水凝胶，该凝胶结合了明胶甲基丙烯酰（GelMA）和聚乙烯醇（PVA），以确保生物相容性的同时增强了药物的控制释放。值得注意的是，它具有良好的储存稳定性、高药物负载能力和高效的吸水性。通过引入 HDAC3 抑制剂 RGFP966，我们可以选择性地抑制 KLB 的激活。这种失活有效地阻断了 FGF21-KLB 信号通路，抑制了 HCC 的进展。重要的是，我们已经在体内和体外成功验证了这一独特现象，为基于水凝胶的抗肿瘤药物输送系统作为 HCC 治疗的一种有前途的策略提供了充分的疗效证据。这一创新性的研究成果为肿瘤治疗领域带来了新的希望，为未来的临床应用提供了可靠的理论基础。
