Zhang Guang-Cong, Song Kang, Wang Xiao-Fan, He Zongyan, Du Jun, Sun Jia-Lei, Xu Ru-Chen, Liu Zhi-Yong, Wang Fu, Qi Zhuo-Ran, Yu Xiang-Nan, Miao Yuqing, Dong Ling, Weng Shu-Qiang, Shen Xi-Zhong, Liu Tao-Tao, Li Yuhao, Zhu Ji-Min
Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Rd., Shanghai 200032, China.
School of Materials and Chemistry, Institute of Bismuth Science, Shanghai Collaborative Innovation Center of Energy Therapy for Tumors, University of Shanghai for Science and Technology, Shanghai 200093, China.
Colloids Surf B Biointerfaces. 2025 Jan;245:114279. doi: 10.1016/j.colsurfb.2024.114279. Epub 2024 Oct 1.
Sorafenib (SOR), a multi-kinase inhibitor for advanced hepatocellular carcinoma (HCC), has limited clinical application due to severe side effects and drug resistance. To overcome these challenges, we developed a bismuth-based nanomaterial (BOS) for thermal injury-assisted continuous targeted therapy in HCC. Initially, the mesoporous nanomaterial was loaded with SOR, forming the BOS@SOR nano-carrier system for drug delivery and controlled release. Notably, compared to targeted or photothermal therapy alone, the combination therapy using this nano-carrier system significantly impaired cell proliferation and increased apoptosis. In vivo efficacy evaluations demonstrated that BOS@SOR exhibited excellent biocompatibility, confirmed through hemolysis and biochemical analyses. Additionally, BOS@SOR enhanced contrast in computed tomography, aiding in the precise identification of HCC size and location. The photothermal therapeutic properties of bismuth further contributed to the synergistic anti-tumor activity of BOS@SOR, significantly reducing tumor growth in an orthotopic xenograft HCC model. Taken together, encapsulating SOR within a bismuth-based mesoporous nanomaterial creates a multifunctional and environmentally stable nanocomposite (BOS@SOR), enhancing the therapeutic effect of SOR and presenting an effective strategy for HCC treatment.
索拉非尼（SOR）是一种用于晚期肝细胞癌（HCC）的多激酶抑制剂，由于严重的副作用和耐药性，其临床应用受到限制。为了克服这些挑战，我们开发了一种基于铋的纳米材料（BOS），用于在肝癌中进行热损伤辅助的持续靶向治疗。最初，介孔纳米材料负载了索拉非尼，形成了用于药物递送和控释的BOS@SOR纳米载体系统。值得注意的是，与单独的靶向治疗或光热治疗相比，使用这种纳米载体系统的联合治疗显著抑制了细胞增殖并增加了细胞凋亡。体内疗效评估表明，BOS@SOR表现出优异的生物相容性，这通过溶血和生化分析得到证实。此外，BOS@SOR增强了计算机断层扫描中的对比度，有助于精确识别肝癌的大小和位置。铋的光热治疗特性进一步促进了BOS@SOR的协同抗肿瘤活性，在原位异种移植肝癌模型中显著降低了肿瘤生长。综上所述，将索拉非尼封装在基于铋的介孔纳米材料中可形成一种多功能且环境稳定的纳米复合材料（BOS@SOR），增强了索拉非尼的治疗效果，并为肝癌治疗提供了一种有效的策略。
