Department of Pharmacy, College of Pharmacy, Kangwon National University, Chuncheon, 24341, Republic of Korea.
Kangwon Institute of Inclusive Technology, Kangwon National University, Chuncheon, 24341, Republic of Korea.
Small. 2024 Nov;20(46):e2400287. doi: 10.1002/smll.202400287. Epub 2024 Aug 7.
This paper introduces catheter-directed intravascular casting hydrogels for transarterial chemo/starvation/chemodynamic embolization (TACSCE) therapy of hepatocellular carcinoma (HCC). Comprising Mn ion-crosslinked hyaluronic acid-dopamine (HD) with glucose oxidase (for glucose decomposition to HO in starvation therapy), doxorubicin (for chemotherapy), and iopamidol (for X-ray imaging), these hydrogels are fabricated for transarterial embolization therapy guided by X-ray fluoroscopy. Mn (from MnO) demonstrates strong coordination with the catechol group of HD, providing hypoxia relief through O generation and cellular glutathione (GSH) consumption, compared to the OH radical generation potential of Mn. The gelation time-controlled, catheter-injectable, and rheologically tuned multitherapeutic/embolic gel system effectively reaches distal arterioles, ensuring complete intravascular casting with fewer complications related to organic solvents. Glucose deprivation, cascade reactive oxygen species (ROS) generation, GSH depletion, and sustained release profiles of multiple drug cargos from the hydrogel system are also achieved. The combined chemo/starvation/chemodynamic efficacies of these designed hydrogel systems are confirmed in HCC cell cultures and HCC-bearing animal models. The developed radiopaque/injectable/embolic/sol-to-gel transformable systems for TACSCE therapy may offer enhanced therapeutic efficacies compared to typical transarterial embolization and transarterial chemoembolization procedures for HCC.
本文介绍了一种用于经动脉化疗/饥饿/化学动力学栓塞（TACSCE）治疗肝细胞癌（HCC）的导管引导的血管内水凝胶。该水凝胶由锰离子交联透明质酸-多巴胺（HD）与葡萄糖氧化酶（用于饥饿治疗中的葡萄糖分解为 HO）、阿霉素（用于化疗）和碘帕醇（用于 X 射线成像）组成，用于 X 射线透视引导的经动脉栓塞治疗。与 Mn 的 OH 自由基生成潜力相比，MnO 中的 Mn 与 HD 的儿茶酚基团具有很强的配位作用，通过生成 O 和消耗细胞谷胱甘肽（GSH）来缓解缺氧。该水凝胶具有凝胶时间可控、导管可注射和流变可调的多治疗/栓塞凝胶系统，可有效到达远端小动脉，确保完全的血管内铸型，减少与有机溶剂相关的并发症。还实现了葡萄糖剥夺、级联活性氧（ROS）生成、GSH 耗竭以及水凝胶系统中多种药物载体的持续释放。在 HCC 细胞培养和 HCC 荷瘤动物模型中证实了这些设计的水凝胶系统的联合化疗/饥饿/化学动力学疗效。与典型的经动脉栓塞和经动脉化疗栓塞治疗 HCC 相比，开发的用于 TACSCE 治疗的放射不透射/可注射/栓塞/溶胶-凝胶转化系统可能具有更高的治疗效果。
