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载药介孔有机硅包覆四氧化三铁磁性纳米颗粒联合碘化油经导管动脉化疗栓塞抑制肝癌进展

Periodic mesoporous organosilica-coated magnetite nanoparticles combined with lipiodol for transcatheter arterial chemoembolization to inhibit the progression of liver cancer.

机构信息

Department of Interventional Therapy, Department of Radiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, Jiangsu, PR China.

Department of Radiology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu, PR China.

出版信息

J Colloid Interface Sci. 2021 Jun;591:211-220. doi: 10.1016/j.jcis.2021.02.022. Epub 2021 Feb 10.

DOI:10.1016/j.jcis.2021.02.022
PMID:33609893
Abstract

Transcatheter arterial chemoembolization (TACE) is standard locoregional therapy for hepatocellular carcinoma (HCC) that involves the injection of chemotherapeutic drugs with embolic agents into tumor tissues through intra-arterial transcatheter infusion. TACE technology using lipiodol emulsion has been most widely used in the treatment of human HCC. However, lipiodol emulsions with anticancer drugs do not stably maintain high drug concentrations at tumor sites. Herein, we developed a dual-modality imaging nanoplatform for the TACE treatment of liver cancer by integrating periodic mesoporous organosilica (PMO) with magnetite (FeO) nanoparticles and Cy5.5 molecules (denoted as FeO@PMO-Cy5.5). FeO@PMO-Cy5.5 showed an excellent doxorubicin (Dox)-loading capacity, sensitive drug release behavior under acidic conditions, and good biocompatibility. Moreover, Cy5.5-mediated optical imaging showed that Dox-loaded FeO@PMO-Cy5.5 (FeO@PMO-Cy5.5-Dox) could enter liver cancer cells and effectively inhibit their growth. In addition, FeO@PMO-Cy5.5-Dox was used in combination with transarterial embolization for the treatment of in situ VX2 liver tumors in rabbits. Magnetic resonance imaging (MRI) evaluation showed that FeO@PMO-Cy5.5-Dox perfused through arteries was deposited into liver tumors, and FeO@PMO-Cy5.5-Dox combined with lipiodol to control liver tumors yielded the optimal therapeutic effect. In addition, histological analysis showed that compared with both lipiodol embolization and traditional lipiodol combined with Dox chemoembolization, FeO@PMO-Cy5.5-Dox combined with lipiodol chemoembolization induced more complete tumor tissue necrosis. In summary, these results indicate that the FeO@PMO-Cy5.5-Dox platform has the potential to become an advanced tool for the transarterial treatment of unresectable liver cancer.

摘要

经导管动脉化疗栓塞术(TACE)是治疗肝细胞癌(HCC)的标准局部区域治疗方法,它涉及通过动脉内经导管输注将化疗药物与栓塞剂注入肿瘤组织中。使用碘油乳剂的 TACE 技术已在治疗人类 HCC 中得到最广泛的应用。然而,载有抗癌药物的碘油乳剂并不能在肿瘤部位稳定地保持高药物浓度。在此,我们通过将介孔有机硅(PMO)与磁铁矿(FeO)纳米粒子和 Cy5.5 分子(表示为 FeO@PMO-Cy5.5)集成,开发了一种用于肝癌 TACE 治疗的双模式成像纳米平台。FeO@PMO-Cy5.5 表现出优异的阿霉素(Dox)负载能力,在酸性条件下具有敏感的药物释放行为,并且具有良好的生物相容性。此外,Cy5.5 介导的光学成像表明,载有 Dox 的 FeO@PMO-Cy5.5(FeO@PMO-Cy5.5-Dox)可以进入肝癌细胞并有效抑制其生长。此外,将 FeO@PMO-Cy5.5-Dox 与经动脉栓塞联合用于治疗兔原位 VX2 肝癌。磁共振成像(MRI)评估表明,通过动脉灌注的 FeO@PMO-Cy5.5-Dox 沉积在肝肿瘤中,并且 FeO@PMO-Cy5.5-Dox 与碘油结合控制肝肿瘤产生了最佳的治疗效果。此外,组织学分析表明,与碘油栓塞和传统碘油联合 Dox 化疗栓塞相比,FeO@PMO-Cy5.5-Dox 联合碘油化疗栓塞诱导了更完全的肿瘤组织坏死。总之,这些结果表明,FeO@PMO-Cy5.5-Dox 平台有可能成为治疗不可切除肝癌的先进经动脉治疗工具。

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