Department of Nanomedicine, Iuliu Hatieganu University of Medicine and Pharmacy, Third Surgery Clinic, Cluj-Napoca, Romania.
Int J Nanomedicine. 2011 Jan 17;6:129-41. doi: 10.2147/IJN.S15841.
The main goal of this investigation was to develop and test a new method of treatment for human hepatocellular carcinoma (HCC). We present a method of carbon nanotube-enhanced laser thermal ablation of HepG2 cells (human hepatocellular liver carcinoma cell line) based on a simple multiwalled carbon nanotube (MWCNT) carrier system, such as human serum albumin (HSA), and demonstrate its selective therapeutic efficacy compared with normal hepatocyte cells. Both HepG2 cells and hepatocytes were treated with HSA-MWCNTs at various concentrations and at various incubation times and further irradiated using a 2 W, 808 nm laser beam. Transmission electron, phase contrast, and confocal microscopy combined with immunochemical staining were used to demonstrate the selective internalization of HSA-MWCNTs via Gp60 receptors and the caveolin-mediated endocytosis inside HepG2 cells. The postirradiation apoptotic rate of HepG2 cells treated with HSA-MWCNTs ranged from 88.24% (for 50 mg/L) at 60 sec to 92.34% (for 50 mg/L) at 30 min. Significantly lower necrotic rates were obtained when human hepatocytes were treated with HSA-MWCNTs in a similar manner. Our results clearly show that HSA-MWCNTs selectively attach on the albondin (aka Gp60) receptor located on the HepG2 membrane, followed by an uptake through a caveolin-dependent endocytosis process. These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating.
本研究的主要目的是开发和测试一种新的人肝癌(HCC)治疗方法。我们提出了一种基于简单的多壁碳纳米管(MWCNT)载体系统(如人血清白蛋白(HSA))增强激光热消融 HepG2 细胞(人肝癌细胞系)的方法,并证明其与正常肝细胞相比具有选择性的治疗效果。用 HSA-MWCNTs 处理 HepG2 细胞和肝细胞,浓度和孵育时间不同,然后用 2 W、808nm 激光照射。透射电子显微镜、相差显微镜和共聚焦显微镜结合免疫化学染色,证明了 HSA-MWCNTs 通过 Gp60 受体的选择性内化以及 HepG2 细胞内的 caveolin 介导的内吞作用。用 HSA-MWCNTs 处理的 HepG2 细胞的辐射后凋亡率范围从 60 秒时的 50mg/L 为 88.24%到 30 分钟时的 50mg/L 为 92.34%。以类似的方式用 HSA-MWCNTs 处理人肝细胞时,得到的坏死率明显较低。我们的结果清楚地表明,HSA-MWCNTs 选择性地附着在位于 HepG2 膜上的白蛋白(又名 Gp60)受体上,然后通过 caveolin 依赖性内吞作用被摄取。这些独特的结果可能代表使用激光加热纳米定位热消融治疗肝癌的重要一步。