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Tat肽-TTA1适配体-聚乙二醇修饰的明胶-硅氧烷纳米颗粒对胶质瘤的高效靶向作用

Highly Efficient Glioma Targeting of Tat Peptide-TTA1 Aptamer-Polyephylene Glycol-Modified Gelatin-Siloxane Nanoparticles.

作者信息

Lin Xiao-Ning, Tian Xinli, Li Wang, Sun Jin, Wei Feng, Feng Wei, Huang Zhi-Chun, Tian Xin-Hua

机构信息

Department of Neurosurgery, Zhongshan Hospital of Xiamen University, Xiamen 361004, China.

Department of Cardiovascular Disease, Chinese People's Liberation Army General Hospital of Beijing Military Region, Beijing 100000, China.

出版信息

J Nanosci Nanotechnol. 2018 Apr 1;18(4):2325-2329. doi: 10.1166/jnn.2018.14379.

Abstract

Gliomas are the most common type of intracranial malignant tumor; however, current treatment approaches are often ineffective due to limited penetration of genes or drugs through the blood-brain barrier (BBB). Here we describe the synthesis of gelatin-siloxane nanoparticles (GS NPs) as candidate gene carriers through a two-step sol-gel process. To increase the efficiency of glioma targeting, human immunodeficiency virus-derived Tat, tumor-targeting aptamer (TTA)1, and polyethylene glycol (PEG) were conjugated to the GS NPs to generate Tat-TTA1-PEG-GS NPs. In vivo imaging revealed that these modified NPs not only evaded capture by the reticulo-endothelial system, but were able to cross the BBB to reach gliomas. Our results suggest that Tat-TTA1-PEG-GS NPs are a new type of non-viral vector that can deliver therapeutic DNA or drugs for highly efficient glioma treatment.

摘要

神经胶质瘤是最常见的颅内恶性肿瘤类型;然而,由于基因或药物透过血脑屏障(BBB)的能力有限,目前的治疗方法往往无效。在此,我们描述了通过两步溶胶-凝胶法合成明胶-硅氧烷纳米颗粒(GS NPs)作为候选基因载体。为了提高神经胶质瘤靶向效率,将源自人类免疫缺陷病毒的Tat、肿瘤靶向适体(TTA)1和聚乙二醇(PEG)与GS NPs偶联,以生成Tat-TTA1-PEG-GS NPs。体内成像显示,这些修饰的纳米颗粒不仅能逃避网状内皮系统的捕获,还能够穿过血脑屏障到达神经胶质瘤。我们的结果表明,Tat-TTA1-PEG-GS NPs是一种新型非病毒载体,可递送治疗性DNA或药物用于高效的神经胶质瘤治疗。

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