摘要
【目的】研究磷酰胆碱修饰的氧化石墨烯作为药物载体经导管动脉化疗栓塞治疗肝癌的安全性和有效性。【方法】制备阿霉素负载的叶酸靶向的磷酰胆碱修饰氧化石墨烯(DOX@GO-PCn-FA)。经新西兰大白兔的耳缘静脉分别注射氧化石墨烯(GO)和DOX@GO-PCn-FA以研究GO和DOX@GO-PCn-FA经静脉注射的安全性和生物分布。取10只雄性新西兰大白兔建立VX2肝癌模型并以动态增强CT扫描明确肿瘤情况。以股动脉入路选择性插管至肝叶或肝段动脉,以数字减影血管造影(DSA)明确肿瘤供血动脉。通过导管注射DOX@GO-PCn-FA对肝癌行选择性栓塞化疗(TACE)。TACE术后第7天行动态增强CT扫描以及主要组织和器官的病理学检查以研究DOX@GO-PCn-FA对肝癌的栓塞效果以及生物分布和安全性。【结果】经静脉注射GO引起显著的血栓形成和肺动脉栓塞,而同等剂量的DOX@GO-PCn-FA未出现这些现象。DOX@GO-PCn-FA用于TACE能有效减少肝脏肿瘤血供。病理学检查可见DOX@GO-PCn-FA主要沉积于肿瘤内,未见明显并发症。【结论】GO-PCn具有良好的生物相容性并能有效地对肝脏肿瘤进行化疗栓塞。
【Objective】To investigate the safety and efficacy of phosphorylcholine oligomer grafted graphene oxide as a drug carrier for transcatheter arterial chemoembolization in the treatment of liver cancer.【Methods】Doxorubicin loaded folic acid labeled phosphorylcholine oligomer grafted graphene oxide(DOX@GO-PCn-FA)was prepared. Graphene oxide(GO)and DOX@GO-PCn-FA were injected intravenously via marginal ear vein in New Zealand white rabbits respectively to assess their safety and biodistribution for intravenous administration. Ten male New Zealand rabbits were used to establishe the VX2 liver cancer model and the tumor characteristics were confirmed by dynamic contrast enhanced CT scan. Catheter was inserted via femoral artery and advanced into hepatic lobar or segmental artery. Digital subtraction angiography(DSA)was performed to validate the tumor feeding vessels. DOX@GO-PCn-FA was injected through the catheter to carry out selective transcatheter arterial chemoembolization(TACE). Dynamic enhanced CT scan and pathological examinations of major tissues and organs were implemented 7 days post TACE to evaluate the efficacy of embolization effect of DOX@GO-PCn-FA against liver tumor as well as the biodistribution and safety.【Results】Intravenous injection of GO resulted in significant thrombosis and pulmonary embolism whereas DOX@GO-PCn-FA of same dosage did not.DOX@GO-PCn-FA was capable of effectively diminishing the blood supply of liver tumors when applied in TACE.Pathologic exploration revealed that DOX@ GO-PCn-FA mainly deposited in the tumor,and no obvious complications were observed. 【Conclusions】 GO-PCn presented superior biocompatibility and exerted effective chemoembolization against liver cancer.
出处
《中山大学学报（医学版）》
CAS
CSCD
北大核心
2018年第1期18-25,共8页
Journal of Sun Yat-Sen University:Medical Sciences
基金
国家自然科学基金面上项目(81671792)
广东省医学科学技术研究基金(A2017025)
关键词
肝癌
氧化石墨烯
磷酰胆碱
经导管动脉化疗栓塞
liver cancer
graphene oxide
phosphorylcholine
transcatheter arterial chemoembolization
