Minimally Invasive Therapeutics Laboratory, Department of Vascular and Interventional Radiology, Mayo Clinic, Phoenix, AZ 85054, USA.
John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Sci Transl Med. 2021 Feb 10;13(580). doi: 10.1126/scitranslmed.abe3889.
Percutaneous locoregional therapies (LRTs), such as thermal ablation, are performed to limit the progression of hepatocellular carcinoma (HCC) and offer a bridge for patients waiting for liver transplantation. However, physiological challenges related to tumor location, size, and existence of multiple lesions as well as safety concerns related to potential thermal injury to adjacent tissues may preclude the use of thermal ablation or lead to its failure. Here, we showed a successful injection of an ionic liquid into tissue under image guidance, ablation of tumors in response to the injected ionic liquid, and persistence (28 days) of coinjected chemotherapy with the ionic liquid in the ablation zone. In a rat HCC model, the rabbit VX2 liver tumor model, and 12 human resected tumors, injection of the ionic liquid led to consistent tumor ablation. Combining the ionic liquid with the chemotherapy agent, doxorubicin, resulted in synergistic cytotoxicity when tested with cultured HCC cells and uniform drug distribution throughout the ablation zone when percutaneously injected into liver tumors in the rabbit liver tumor model. Because this ionic liquid preparation is simple to use, is efficacious, and has a low cost, we propose that this new LRT may bridge more patients to liver transplantation.
经皮局部区域治疗(LRT),如热消融,可用于限制肝细胞癌(HCC)的进展,并为等待肝移植的患者提供桥梁。然而,与肿瘤位置、大小以及多个病变的存在相关的生理挑战,以及与潜在热损伤相邻组织相关的安全问题,可能会排除使用热消融或导致其失败。在这里,我们在影像引导下成功地将一种离子液体注入组织中,注射离子液体后肿瘤被消融,并且化疗药物与离子液体的共注射在消融区域中持续存在(28 天)。在大鼠 HCC 模型、兔 VX2 肝癌模型和 12 个人体切除的肿瘤中,离子液体的注射导致了一致的肿瘤消融。当将离子液体与化疗药物阿霉素联合使用时,在培养的 HCC 细胞中测试时具有协同的细胞毒性,并且当经皮注射到兔肝癌模型中的肝肿瘤中时,药物在整个消融区域中均匀分布。由于这种离子液体制剂使用简单、有效且成本低,我们提出这种新的 LRT 可能会为更多的患者提供肝移植的机会。