石墨烯基纳米药物经导管动脉化疗栓塞治疗原发性肝癌

经导管动脉化疗栓塞术（TACE）是无法切除的肝癌的首选疗法。由于肝癌细胞固有耐药、化疗药在肿瘤细胞内存留时间短、碘油/化疗药乳化剂的不稳定性等原因，TACE术后肝癌细胞坏死不完全，导致治疗失败。具有超高比表面积的石墨烯基纳米材料如氧化石墨烯（graphene oxide，GO）作为药物载体受到广泛的关注。我们在前期试验中发现，GO在碘油中具有极佳的分散性，作为载体能稳定地将水溶性化疗药物均匀分散于碘油中。在细胞实验中，我们发现GO可显著增强化疗药对肿瘤细胞的杀伤作用。然而，文献报道以及我们的前期研究【Carbon，2014】和预实验均发现，GO有明显的细胞毒性，限制了其经常规给药途径的应用。本项目将在前期研究基础上，采用体内外模型，以碘化油和药物洗脱微球为对照，通过介入的方法充分利用GO的载体性和细胞毒性，深入研究GO负载阿霉素在TACE治疗肝癌中的效果，为提高TACE的疗效提供新的思路。

Transcatheter arterial chemoembolization (TACE) is the first choice of treatment for unresectable hepatocellular carcinoma (HCC). Due to the inherent chemoresistance of liver cancer cells, short retention period of chemotherapeutic agents inside the tumor cells, and poor stability of lipiodol/chemotherapeutic agents emulsion, et.al, incomplete necrosis of cancer cells after TACE treatment ultimately leads to the failure of therapy. With ultra-high surface area, graphene based nanomaterials such as graphene oxide (GO) received widespread attention as vehicle for drug delivery. In our preliminary test we found that GO presented excellent dispersibility in iodized oil, which stably and uniformly dispersed water-soluble chemotherapeutic agent in Lipiodol as a vehicle. In the cell experiments, we found that graphene oxide remarkably enhanced the cytotoxicity effect of chemotherapy agents on tumor cells. Yet, it has been reported and our previous studies [Carbon，2014] and preliminary experiment revealed that GO exerted significant cytotoxicity, limiting its application via conventional route of administration. Based on the preliminary study, by employing in vitro and in vivo models, this project will take the full advantages of GO's capability of vector and cytotoxicity with the method of interventional radiology to further investigate the therapeutic efficacy of doxorubicin-loaded graphene oxide TACE in the treatment of HCC as compared to lipiodol and drug eluting beads, providing new directions to improve the therapeutic effect of TACE.