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用共负载微小RNA - 122和阿霉素的功能化金纳米笼对肝细胞癌进行三联疗法

Triple therapy of hepatocellular carcinoma with microRNA-122 and doxorubicin co-loaded functionalized gold nanocages.

作者信息

Huang Shengnan, Liu Ying, Xu Xin, Ji Mengfei, Li Yuanmin, Song Chengjun, Duan Shaofeng, Hu Yurong

机构信息

Henan Province Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China.

出版信息

J Mater Chem B. 2018 Apr 21;6(15):2217-2229. doi: 10.1039/c8tb00224j. Epub 2018 Apr 3.

Abstract

A combination of different therapy strategies has great potential to efficaciously treat malignant tumors, by virtue of their synergetic effects. Herein, a co-delivery system based on gold nanocages (AuNCs) was designed to deliver both doxorubicin (DOX) and microRNA-122 mimic (miR-122) for an enhanced cancer therapy. DOX was loaded into the AuNCs and miR-122 was condensed onto the surface of the functionalized AuNCs by an electrostatic interaction. Polyethyleneglycol (PEG) and hyaluronic acid (HA) were also introduced to the co-delivery system for targeted drug delivery. We evaluated the cellular uptake, biodistribution and anti-tumor effect in vitro and in vivo. Our results demonstrated an effective delivery of DOX and miR-122 into tumor cells and the tumor tissue. Importantly, the triple therapy, namely the combination of chemotherapy, gene therapy and photothermal therapy, mediated by this multifunctional drug delivery system, exhibited better anti-tumor effect than any single therapy, both in vitro and in vivo. Additionally, this drug delivery system caused insignificant toxicity to the major organs and had no obvious effect on the body weight of the mice. It could be concluded that multifunctional AuNCs are promising as a co-delivery vector for an enhanced anti-tumor effect.

摘要

不同治疗策略的组合因其协同效应而具有有效治疗恶性肿瘤的巨大潜力。在此,设计了一种基于金纳米笼(AuNCs)的共递送系统,用于同时递送阿霉素(DOX)和微小RNA-122模拟物(miR-122),以增强癌症治疗效果。DOX被装载到AuNCs中,miR-122通过静电相互作用凝聚在功能化AuNCs的表面。聚乙二醇(PEG)和透明质酸(HA)也被引入到共递送系统中以实现靶向药物递送。我们评估了其在体外和体内的细胞摄取、生物分布及抗肿瘤效果。我们的结果表明DOX和miR-122能有效递送至肿瘤细胞和肿瘤组织中。重要的是,由这种多功能药物递送系统介导的三联疗法,即化疗、基因治疗和光热治疗的联合,在体外和体内均表现出比任何单一疗法更好的抗肿瘤效果。此外,这种药物递送系统对主要器官的毒性不显著,对小鼠体重也没有明显影响。可以得出结论,多功能AuNCs作为一种增强抗肿瘤效果的共递送载体具有广阔前景。

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