Peng Yisheng, Liu Hui, Liang Xiaoliu, Cao Lei, Teng Minglei, Chen Hu, Li Zhenjie, Peng Xuqi, Mao Jingsong, Cheng Hongwei, Liu Gang
State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, Fujian Engineering Research Center of Molecular Theranostic Technology, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
College of Pharmacy, Guangxi Medical University, Nanning 530021, China.
J Control Release. 2025 Apr 10;380:1-16. doi: 10.1016/j.jconrel.2025.01.088. Epub 2025 Feb 3.
Hydrogel, as a promising embolic material for hepatocellular carcinoma (HCC), may fully embolize both major vessels and peripheral microvessels. A self-assembling hydrogel composed of chemotherapeutic drugs offers significant clinical benefits without carrier introduction. Herein, we developed a sustained drug-releasing complex hydrogel (RKT@gel), which was fabricated by the self-assembly of raltitrexed chemotherapeutic drugs (R@gel), along with the incorporation of kaempferol and tantalum nanoparticles (Ta NPs). Kaempferol enhances the mechanical strength of R@gel and inhibits hypoxia-induced angiogenesis post-embolization, improving embolization effectiveness. In addition to enabling X-ray-guided transarterial chemoembolization (TACE), Ta NPs enhance radiation sensitivity. These synergistic effects of RKT@gel not only significantly induce immunogenic cell death, thereby enhancing the activation of dendritic cells, but also activate major histocompatibility complex class I (MHC-I)-mediated antitumor immune recognition and cytotoxicity. In vivo, RKT@gel achieves enhanced tumor deposition and sustained drug release, effectively suppressing tumor progression. Additionally, when combined with radiotherapy, RKT@gel achieves efficient antitumor immunoactivation. Overall, this versatile composite hydrogel not only achieves effective embolization therapy but also substantially triggers antitumor immune responses with good biocompatibility. This multifunctional design provides a TACE-based multidisciplinary strategy for HCC.
水凝胶作为一种很有前景的肝细胞癌（HCC）栓塞材料，可完全栓塞主要血管和外周微血管。由化疗药物组成的自组装水凝胶无需引入载体即可带来显著的临床益处。在此，我们开发了一种持续释药复合水凝胶（RKT@gel），它由雷替曲塞化疗药物自组装形成（R@gel），并加入了山柰酚和钽纳米颗粒（Ta NPs）。山柰酚增强了R@gel的机械强度，并抑制栓塞后缺氧诱导的血管生成，提高了栓塞效果。除了实现X射线引导下的经动脉化疗栓塞（TACE）外，Ta NPs还增强了放射敏感性。RKT@gel的这些协同效应不仅能显著诱导免疫原性细胞死亡，从而增强树突状细胞的活化，还能激活主要组织相容性复合体I类（MHC-I）介导的抗肿瘤免疫识别和细胞毒性。在体内，RKT@gel实现了增强的肿瘤沉积和持续的药物释放，有效抑制了肿瘤进展。此外，当与放疗联合使用时，RKT@gel实现了高效的抗肿瘤免疫激活。总体而言，这种多功能复合水凝胶不仅实现了有效的栓塞治疗，还以良好的生物相容性显著触发了抗肿瘤免疫反应。这种多功能设计为HCC提供了一种基于TACE的多学科策略。
