In vitro and in vivo optimization of liposomal nanoparticles based brain targeted vgf gene therapy.
In vitro and in vivo optimization of liposomal nanoparticles based brain targeted vgf gene therapy.
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DOI：
10.1016/j.ijpharm.2021.121095
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发表时间：
2021-10-25
影响因子：
5.8
通讯作者：
Singh J
中科院分区：
文献类型：
--
作者：
Arora S;Singh J
Vgf（non-acronymic）是一种神经营养因子刺激的蛋白质，在学习、突触活动和神经发生中起关键作用，在阿尔茨海默病（AD）患者的脑中显著下调。然而，由于vgf是一个大的极性蛋白，一个安全和有效的基因传递载体是其通过血脑屏障（BBB）的关键。这项研究工作展示了脑靶向脂质体纳米颗粒，其优化用于递送编码vgf的质粒穿过BBB并捕获脑细胞。使用葡萄糖转运蛋白-1靶向配体（甘露糖）和脑靶向细胞穿透肽（嵌合狂犬病病毒糖蛋白片段、狂犬病病毒衍生肽、穿透肽或CGNHPHLAKYNGT肽）通过表面功能化实现脑靶向。配体通过亲核取代反应与脂质结合，结合效率超过75%。通过膜水合技术形成脂质体，证明尺寸小于200 nm，正ζ电位（15-20 mV）和多分散指数小于0.3。双功能化脂质体显示出~3 pg/μg蛋白质vgf跨体外BBB的转染，以及~80 pg/mg蛋白质在小鼠脑中的转染，这与未处理的对照相比高1.5-2倍（p<0.05）。该纳米颗粒在体内外也具有生物相容性，表明了一种安全有效的基因递送系统来治疗AD。
Vgf (non-acronymic), a neurotrophin stimulated protein which plays a crucial role in learning, synaptic activity, and neurogenesis, is markedly downregulated in the brain of Alzheimer’s disease (AD) patients. However, since vgf is a large polar protein, a safe and efficient gene delivery vector is critical for its delivery across the blood brain barrier (BBB). This research work demonstrates brain-targeted liposomal nanoparticles optimized for delivering plasmid encoding vgf across BBB and transfecting brain cells. Brain targeting was achieved by surface functionalization using glucose transporter-1 targeting ligand (mannose) and brain targeted cell-penetrating peptides (chimeric rabies virus glycoprotein fragment, rabies virus derived peptide, penetratin peptide, or CGNHPHLAKYNGT peptide). The ligands were conjugated to lipid via nucleophilic substitution reaction resulting in more than 75% binding efficiency. The liposomes were formed by film hydration technique demonstrating size less than 200 nm, positive zeta potential (15–20 mV), and polydispersity index less than 0.3. The bifunctionalized liposomes demonstrated ~3 pg/µg protein vgf transfection across in vitro BBB, and ~80 pg/mg protein in mice brain which was 1.5–2 fold (p<0.05) higher compared to untreated control. The nanoparticles were also biocompatible in vitro and in vivo, suggesting a safe and efficient gene delivery system to treat AD.
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影响因子：
46.2
作者：
Behzadi S;Serpooshan V;Tao W;Hamaly MA;Alkawareek MY;Dreaden EC;Brown D;Alkilany AM;Farokhzad OC;Mahmoudi M
通讯作者：
Mahmoudi M
DOI：
10.1523/jneurosci.3145-08.2008
发表时间：
2008-09-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bozdagi O;Rich E;Tronel S;Sadahiro M;Patterson K;Shapiro ML;Alberini CM;Huntley GW;Salton SR
通讯作者：
Salton SR
影响因子：
8
作者：
Fröhlich E
通讯作者：
Fröhlich E
影响因子：
2.4
作者：
Cocco, Cristina;D'Amato, Filomena;Ferri, Gian-Luca
通讯作者：
Ferri, Gian-Luca
影响因子：
4.2
作者：
Biemans EALM;Jäkel L;de Waal RMW;Kuiperij HB;Verbeek MM
通讯作者：
Verbeek MM