Insulin-coated gold nanoparticles as an effective approach for bypassing the blood-brain barrier

Author(s):  
Oshra Betzer ◽  
Malka Shilo ◽  
Menachem Motiei ◽  
Rachela Popovtzer
2015 ◽  
Vol 12 (11) ◽  
pp. 4137-4145 ◽  
Author(s):  
Itsaso Cabezón ◽  
Gemma Manich ◽  
Raquel Martín-Venegas ◽  
Antoni Camins ◽  
Carme Pelegrí ◽  
...  

2015 ◽  
Vol 13 (1) ◽  
Author(s):  
Hagit Sela ◽  
Hagit Cohen ◽  
Paz Elia ◽  
Raya Zach ◽  
Zeev Karpas ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Viktoriya Sokolova ◽  
Gehad Mekky ◽  
Selina Beatrice van der Meer ◽  
Michael C. Seeds ◽  
Anthony J. Atala ◽  
...  

Abstract The blood–brain barrier (BBB) is an efficient barrier for molecules and drugs. Multicellular 3D spheroids display reproducible BBB features and functions. The spheroids used here were composed of six brain cell types: Astrocytes, pericytes, endothelial cells, microglia cells, oligodendrocytes, and neurons. They form an in vitro BBB that regulates the transport of compounds into the spheroid. The penetration of fluorescent ultrasmall gold nanoparticles (core diameter 2 nm; hydrodynamic diameter 3–4 nm) across the BBB was studied as a function of time by confocal laser scanning microscopy, with the dissolved fluorescent dye (FAM-alkyne) as a control. The nanoparticles readily entered the interior of the spheroid, whereas the dissolved dye alone did not penetrate the BBB. We present a model that is based on a time-dependent opening of the BBB for nanoparticles, followed by a rapid diffusion into the center of the spheroid. After the spheroids underwent hypoxia (0.1% O2; 24 h), the BBB was more permeable, permitting the uptake of more nanoparticles and also of dissolved dye molecules. Together with our previous observations that such nanoparticles can easily enter cells and even the cell nucleus, these data provide evidence that ultrasmall nanoparticle can cross the blood brain barrier.


2020 ◽  
Vol 8 ◽  
pp. 100072
Author(s):  
F.U. Rehman ◽  
J. Bao ◽  
P. Muhammad ◽  
W. He ◽  
S. Hanif ◽  
...  

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Yanhua Zhang ◽  
Janelle Buttry Walker ◽  
Zeljka Minic ◽  
Fangchao Liu ◽  
Harry Goshgarian ◽  
...  

2020 ◽  
Vol 9 (1) ◽  
pp. 155 ◽  
Author(s):  
Rodriguez-Izquierdo I ◽  
Serramia MJ ◽  
Gomez R ◽  
De La Mata FJ ◽  
Bullido MJ ◽  
...  

Infections caused by HSV-1 and their typical outbreaks invading the nervous system have been related to neurodegenerative diseases. HSV-1 infection may deregulate the balance between the amyloidogenic and non-amyloidogenic pathways, raising the accumulation of amyloid-β peptides, one of the hallmarks in the neurodegenerative diseases. An effective treatment against both, HSV-1 infections and neurodegeneration, is a major therapeutic target. Therefore, gold nanoparticles (NPAus) have been previously studied in immunotherapy, cancer and cellular disruptions with very promising results. Our study demonstrates that a new NPAus family inhibits the HSV-1 infection in a neural-derived SK-N-MC cell line model and that this new NPAus reduces the HSV-1-induced β-secretase activity, as well as amyloid-β accumulation in SK-APP-D1 modifies cell line. We demonstrated that NPAuG3-S8 crosses the blood-brain barrier (BBB) and does not generate cerebral damage to in vivo CD1 mice model. The NPAuG3-S8 could be a promising treatment against neuronal HSV-1 infections and neuronal disorders related to the Aβ peptides.


2013 ◽  
Vol 1 (8) ◽  
pp. 824 ◽  
Author(s):  
Christian Freese ◽  
Ronald E. Unger ◽  
Robert C. Deller ◽  
Matthew I. Gibson ◽  
Christoph Brochhausen ◽  
...  

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Skylar T Chuang ◽  
Siobanth Cruz ◽  
Julia Stab ◽  
Sylvia Wagner ◽  
Hagen Von Briesen ◽  
...  

The overall objective of this study was to develop a HDL-based multifunctional platform for transport and delivery of highly hydrophobic gold nanoparticles (AuNP) bearing photothermic properties across the blood brain barrier (BBB). We exploited the ability of apolipoprotein E3 (apoE3) to act as a high affinity ligand for the low-density lipoprotein receptor to gain entry into endothelial and glioblastoma cells. The issue of poor aqueous solubility of AuNP of varying diameters (3, 10, or 10 nm) was overcome by integrating them with phospholipids and apoE3, yielding reconstituted rHDL bearing AuNP (rHDL-AuNP). Transmission electron microscopy (TEM) revealed the presence of AuNP embedded in spherical particles. Incubation of human brain microvasculature endothelial cells or glioblastoma cells with rHDL-AuNP bearing unlabeled or FITC-labeled apoE3 revealed robust uptake of particles that were localized in endocytic/lysosomal vesicles. The transport of rHDL-AuNP across an in vitro BBB model developed from primary porcine endothelial cells was examined. The addition of rHDL-AuNP to the luminal side of the cells did not affect the integrity of the BBB as assessed by the localization of key tight junction markers such as occludin, claudins and ZO-1 by immunofluorescence, and, by continual measurement of the transepithelial electrical resistance by impedance spectroscopy under physiological conditions. Lastly, the appearance of fluorescein fluorescence and AuNP in the abluminal side suggested transport of rHDL-AuNP across the neurovascular junction. These findings demonstrate that rHDL bearing apoE3 acts as a detergent in solubilizing and dramatically improving the aqueous solubility of AuNP, facilitates cellular uptake and transcellular transport of rHDL-AuNP across endothelial cells. They are significant since they present rHDL bearing apoE3 as an effective platform for delivering AuNP across the BBB.


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