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新型植物病毒纳米颗粒递送多柔比星增强抗肿瘤疗效并降低心脏毒性。

Enhanced anti-tumor efficacy and reduced cardiotoxicity of doxorubicin delivered in a novel plant virus nanoparticle.

机构信息

Plant Virology Research Center, College of Agriculture, Shiraz University, Shiraz, Iran.

Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Colloids Surf B Biointerfaces. 2019 Feb 1;174:80-86. doi: 10.1016/j.colsurfb.2018.11.008. Epub 2018 Nov 6.

DOI:10.1016/j.colsurfb.2018.11.008
PMID:30445253
Abstract

Plant viruses are one of the newly applied nanoparticles as drug delivery vehicles. Here, we investigated drug delivery performance of Johnson grass chlorotic stripe mosaic virus (JgCSMV) conjugated to folic acid (FA) for targeted delivery of doxorubicin (Dox). The FA-JgCSMV-Dox complex was synthesized and characterized using spectrophotometry, native and denaturing gel electrophoresis and transmission electron microscopy, which disclosed that JgCSMV virions encapsulated Dox and showed comparable size and morphology to the native particles. The JgCSMV nanoparticles loaded with Dox showed a sustained drug release profile in tumor tissue and improved the uptake of Dox in breast cancer cells, leading to enhanced tumor homing. Lastly, we demonstrated that FA-JgCSMV-Dox reduced the tumor growth and cardiotoxicity of athymic mice bearing human breast cancer xenografts in comparison to free Dox. This study is the first report on applicability of JgCSMV for Dox delivery with superior benefits over generally marketed formulations of doxorubicin.

摘要

植物病毒是新兴的纳米颗粒药物递送载体之一。在这里,我们研究了与叶酸(FA)缀合的约翰逊草黄条纹花叶病毒(JgCSMV)作为阿霉素(Dox)靶向递送的药物递送性能。使用分光光度法、天然和变性凝胶电泳以及透射电子显微镜对 FA-JgCSMV-Dox 复合物进行了合成和表征,结果表明 JgCSMV 病毒粒子包封了 Dox,并且与天然颗粒具有相当的大小和形态。载有 Dox 的 JgCSMV 纳米颗粒在肿瘤组织中表现出持续的药物释放曲线,并增加了乳腺癌细胞对 Dox 的摄取,从而增强了肿瘤归巢。最后,我们证明与游离 Dox 相比,FA-JgCSMV-Dox 减少了荷有人乳腺癌异种移植物的无胸腺小鼠的肿瘤生长和心脏毒性。这项研究是关于 JgCSMV 用于 Dox 递送的适用性的首次报告,其优于一般市售的阿霉素制剂。

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