Bijukumar Divya, Girish C M, Sasidharan Abhilash, Nair Shantikumar, Koyakutty Manzoor
Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Cochin 682041, India.
ACS Biomater Sci Eng. 2015 Dec 14;1(12):1211-1219. doi: 10.1021/acsbiomaterials.5b00184. Epub 2015 Nov 18.
Radiofrequency ablation (RFA) is a clinically established therapy for hepatocellular carcinoma (HCC). However, because of poor radio-thermal conductivity of liver tissues, RFA is less efficient against relatively larger (>5 cm) liver tumors. Recently, nanoparticle-enabled RFA has emerged as a better strategy. On the basis of our recent understanding on biodegradability and novel electrothermal properties of graphene, herein, we report development of transferrin conjugated, biodegradable graphene (TfG) for RFA therapy. Cellular uptake studies using confocal microscopy and Raman imaging revealed significantly higher TfG uptake by HCC cells compared to bare graphene. TfG-treated cancer cells upon 5 min exposure to 100 W, 13.5 MHz RF showed >85% cell death, which was 4 times greater than bare graphene. Further evaluation in 3D (3 Dimensional) HCC culture system as well as in vivo rat models demonstrated uniform destruction of tumor cells throughout the 3D microenvironment. This study reveals the potential of molecularly targeted graphene for augmented RFA therapy of liver tumor.
射频消融（RFA）是一种临床上已确立的肝细胞癌（HCC）治疗方法。然而，由于肝组织的射频热传导性较差，RFA对相对较大（>5厘米）的肝肿瘤疗效较低。最近，基于纳米颗粒的RFA已成为一种更好的策略。基于我们最近对石墨烯的生物可降解性和新型电热特性的认识，在此我们报告了用于RFA治疗的转铁蛋白共轭、可生物降解石墨烯（TfG）的研发。使用共聚焦显微镜和拉曼成像进行的细胞摄取研究表明，与裸石墨烯相比，HCC细胞对TfG的摄取显著更高。经TfG处理的癌细胞在暴露于100 W、13.5 MHz射频5分钟后，细胞死亡率>85%，这是裸石墨烯的4倍。在三维（3D）HCC培养系统以及体内大鼠模型中的进一步评估表明，肿瘤细胞在整个3D微环境中被均匀破坏。这项研究揭示了分子靶向石墨烯在增强肝肿瘤RFA治疗方面的潜力。
