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基于超顺磁性氧化铁纳米壳和聚乙烯醇的化疗栓塞系统经动脉给药治疗肝肿瘤

Intra-arterial delivery of superparamagnetic iron-oxide nanoshell and polyvinyl alcohol based chemoembolization system for the treatment of liver tumor.

作者信息

Liang Qi, Wang Yi-Xiang, Ding Jin-Song, He Wei, Deng Ling-Ling, Li Na, Liao Yun-Jie, Li Zhen, Ye Bin, Wang Wei

机构信息

Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.

Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.

出版信息

Discov Med. 2017 Jan;23(124):27-39.

Abstract

A superparamagnetic iron oxide (SPIO) nanoshell and polyvinyl alcohol (PVA) based chemoembolization system for anti-cancer drug doxorubicin (DOX) delivery has previously been presented. We have also previously confirmed the feasibility and safety of this multifunctional system for carrying both DOX and SPIO nanoparticles in vitro. However, the pharmacokinetic and the therapeutic efficacy of this novel drug-delivery system in vivo is not yet clear, and as such was the subject of this study. A rabbit liver tumor model was utilized, whereby the tumors were targeted by SPIO/DOX/PVA composite infused via a catheter into the hepatic arteries which supplying blood to the tumor. The result was compared to saline, DOX+PVA, or SPIO/DOX infusion alone. SPIO/DOX/PVA displayed sustained chemotherapeutic agent release into the tumor. In comparison to other treatment groups, tumor growth rate was significantly slowed down by SPIO/DOX/PVA with a smaller tumor volume and a prolonged survival time of the experimental rabbits. Liver function results demonstrated SPIO/DOX/PVA has no apparent toxicity to the normal liver. Pharmacokinetic studies and histological evaluations in SPIO/DOX/PVA group revealed that long-term retention and drug release within the tumor associated with SPIO/DOX/PVA therapy, and thereafter induced significantly enhanced tumor necrosis and apoptosis. We conclude SPIO/DOX/PVA provides a highly effective therapeutic strategy for management of liver tumors.

摘要

先前已提出一种基于超顺磁性氧化铁(SPIO)纳米壳和聚乙烯醇(PVA)的化疗栓塞系统,用于递送抗癌药物阿霉素(DOX)。我们之前也已证实该多功能系统在体外携带DOX和SPIO纳米颗粒的可行性和安全性。然而,这种新型药物递送系统在体内的药代动力学和治疗效果尚不清楚,因此本研究以此为主题。使用兔肝肿瘤模型,通过导管将SPIO/DOX/PVA复合物注入为肿瘤供血的肝动脉,从而靶向肿瘤。将结果与单独输注生理盐水、DOX+PVA或SPIO/DOX进行比较。SPIO/DOX/PVA显示化疗药物持续释放到肿瘤中。与其他治疗组相比,SPIO/DOX/PVA显著减缓了肿瘤生长速度,减小了肿瘤体积,延长了实验兔的存活时间。肝功能结果表明SPIO/DOX/PVA对正常肝脏无明显毒性。SPIO/DOX/PVA组的药代动力学研究和组织学评估显示,SPIO/DOX/PVA治疗与肿瘤内的长期滞留和药物释放相关,进而显著增强了肿瘤坏死和凋亡。我们得出结论,SPIO/DOX/PVA为肝肿瘤的治疗提供了一种高效的治疗策略。

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