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Comparison of in vivo targeting ability between cRGD and collagen-targeting peptide conjugated nano-carriers for atherosclerosis
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2017-11-22 , DOI: 10.1016/j.jconrel.2017.11.033
Manse Kim , Abhishek Sahu , Gi Beom Kim , Gi Hoon Nam , Wooram Um , So Jin Shin , Yong Yeon Jeong , In-San Kim , Kwangmeyung Kim , Ick Chan Kwon , Giyoong Tae

Atherosclerosis plaque is a major cause of cardiovascular diseases across the globe and a silent killer. There are no physical symptoms of the disease in its early stage and current diagnostic techniques cannot detect the small plaques effectively or safely. Plaques formed in blood vessels can cause serious clinical problems such as impaired blood flow or sudden death, regardless of their size. Thus, detecting early stage of plaques is especially more important to effectively reduce the risk of atherosclerosis. Nanoparticle based delivery systems are recognized as a promising option to fight against this disease, and various targeting ligands are typically used to improve their efficiency. So, the choice of appropriate targeting ligand is a crucial factor for optimal targeting efficiency. cRGD peptide and collagen IV targeting peptide, which binds with the αvβ3 integrin overexpressed in the neovasculature of the plaque and collagen type IV present in the plaque, respectively, are frequently used for the targeting of nanoparticles. However, at present no study has directly compared these two peptides. Therefore, in this study, we have prepared cRGD or collagen IV targeting (Col IV-tg-) peptide conjugated and iron oxide nanoparticle (IONP) loaded Pluronic based nano-carriers for systemic comparison of their targeting ability towards in vivo atherosclerotic plaque in Apolipoprotein E deficient (Apo E−/−) mouse model. Nano-carriers with similar size, surface charge, and IONP loading content but with different targeting ligands were analyzed through in vitro and in vivo experiments. Near infrared fluorescence imaging and magnetic resonance imaging techniques as well as Prussian blue staining were used to compare the accumulation of different ligand conjugated nano-caariers in the aorta of atherosclerotic mice. Our results indicate that cRGD based targeting is more efficient than Col IV-tg-peptide in the early stage of atherosclerosis.



中文翻译:

cRGD和胶原靶向肽缀合的纳米载体在动脉粥样硬化中的体内靶向能力比较

动脉粥样硬化斑块是全球心血管疾病的主要原因,也是沉默的杀手。该疾病在早期没有任何物理症状,目前的诊断技术无法有效或安全地检测出小斑块。无论大小如何,血管中形成的斑块都会引起严重的临床问题,例如血流受损或猝死。因此,检测斑块的早期阶段对于有效降低动脉粥样硬化的风险尤为重要。基于纳米颗粒的递送系统被认为是对抗这种疾病的一种有前途的选择,并且通常使用各种靶向配体来提高其效率。因此,选择合适的靶向配体是获得最佳靶向效率的关键因素。cRGD肽和IV型胶原靶向肽,v β 3整联过表达的在牙斑和型胶原存在于斑块IV的新脉管系统,分别被频繁地用于纳米粒子的靶向。但是,目前尚无研究直接比较这两种肽。因此,在这项研究中,我们制备了结合了cRGD或胶原IV靶向(Col IV-tg-)肽和负载铁氧化物纳米颗粒(IONP)的Pluronic纳米载体,用于系统比较它们对载脂蛋白体内动脉粥样斑块的靶向能力E缺陷(Apo E -/-)小鼠模型。通过体外体外分析了尺寸,表面电荷和IONP负载量相似但靶向配体不同的纳米载体体内实验。近红外荧光成像和磁共振成像技术以及普鲁士蓝染色被用来比较动脉粥样硬化小鼠主动脉中不同配体结合的纳米caerars的积累。我们的结果表明,基于cRGD的靶向在动脉粥样硬化的早期比Col IV-tg-肽更有效。

更新日期:2017-11-22
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