Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
Department of Biomedical Engineering, National University of Singapore, Engineering Drive 3, Engineering Block 4, #04-08, 117583 Singapore.
ACS Biomater Sci Eng. 2021 Dec 13;7(12):5642-5653. doi: 10.1021/acsbiomaterials.1c01005. Epub 2021 Nov 4.
Transarterial chemoembolization (TACE) has emerged as the mainstay treatment for patients suffering from unresectable intermediate hepatocellular carcinoma and also holds the potential to treat other types of hypervascular cancers such as renal cell carcinoma. However, an model for evaluating both embolic performance and drug-release kinetics of the TACE embolic agents is still lacking since the current models greatly simplified the vascular systems as well as the extracellular matrices (ECM) in the organs. Here, we developed a decellularized organ model with preserved ECM and vasculatures as well as a translucent appearance to investigate chemoembolization performances of a clinically widely used embolic agent, i.e., a doxorubicin-loaded ethiodised oil (EO)-based emulsion. We, for the first time, utilized an model to evaluate the liquid-based embolic agent in two organs, i.e., liver and kidneys. We found that the EO-based emulsion with enhanced stability by incorporating an emulsifier, i.e., hydrogenated castor oil-40 (HCO), showed an enhanced occlusion level and presented sustained drug release in the liver model, suggesting an advantageous therapeutic effect for TACE treatment of hepatocellular carcinoma. In contrast, we observed that drug-release burst happened when applying the same therapy in the kidney model even with the HCO emulsifier, which may be explained by the presence of the specific renal vasculature and calyceal systems, indicating an unfavorable effect in the renal tumor treatment. Such an model presents a promising template for chemoembolization evaluation before experiments for the development of novel embolic agents.
经导管动脉化疗栓塞术 (TACE) 已成为治疗不可切除的中晚期肝细胞癌的主要方法,也有潜力治疗其他类型的富血管性癌症,如肾细胞癌。然而,目前的模型大大简化了血管系统以及器官中的细胞外基质 (ECM),因此仍然缺乏评估 TACE 栓塞剂栓塞性能和药物释放动力学的模型。在这里,我们开发了一种去细胞化的器官模型,保留了 ECM 和脉管系统,并且具有半透明的外观,以研究一种临床广泛使用的栓塞剂,即载多柔比星的碘化油 (EO) 基乳剂的化疗栓塞性能。我们首次利用 模型在两个器官(肝脏和肾脏)中评估了基于液体的栓塞剂。我们发现,通过加入乳化剂氢化蓖麻油 40 (HCO) 增强稳定性的 EO 基乳剂在肝脏模型中显示出增强的闭塞水平和持续的药物释放,提示对于 TACE 治疗肝细胞癌具有有利的治疗效果。相比之下,当在肾脏模型中应用相同的治疗方法时,我们观察到药物释放爆发,即使加入 HCO 乳化剂也是如此,这可能是由于存在特定的肾脏脉管系统和肾盏系统所导致的,表明在肾脏肿瘤治疗中效果不理想。这种 模型为新型栓塞剂的开发提供了一个有前途的化疗栓塞评估模板。