scholarly journals Transporter protein and drug-conjugated gold nanoparticles capable of bypassing the blood-brain barrier

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Yanhua Zhang ◽  
Janelle Buttry Walker ◽  
Zeljka Minic ◽  
Fangchao Liu ◽  
Harry Goshgarian ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Transporter Protein ◽  
Blood Brain

scholarly journals Trafficking of Gold Nanoparticles Coated with the 8D3 Anti-Transferrin Receptor Antibody at the Mouse Blood–Brain Barrier

2015 ◽  
Vol 12 (11) ◽  
pp. 4137-4145 ◽  
Author(s):  
Itsaso Cabezón ◽  
Gemma Manich ◽  
Raquel Martín-Venegas ◽  
Antoni Camins ◽  
Carme Pelegrí ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Blood Brain Barrier ◽  
Transferrin Receptor ◽  
Brain Barrier ◽  
Mouse Blood ◽  
Receptor Antibody ◽  
Blood Brain

scholarly journals Spontaneous penetration of gold nanoparticles through the blood brain barrier (BBB)

2015 ◽  
Vol 13 (1) ◽  
Author(s):  
Hagit Sela ◽  
Hagit Cohen ◽  
Paz Elia ◽  
Raya Zach ◽  
Zeev Karpas ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain

scholarly journals EXTH-21. DIFFERENTIAL PROTEIN EXPRESSION LEVELS OF ABC AND SOLUTE CARRIER TRANSPORTERS AT THE BLOOD-BRAIN BARRIER OF HUMAN BRAIN AND GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi86-vi86
Author(s):  
Xun Bao ◽  
Jianmei Wu ◽  
Youming Xie ◽  
Seongho Kim ◽  
Sharon Michelhaugh ◽  
...  
Keyword(s):  
Protein Expression ◽  
Human Brain ◽  
Blood Brain Barrier ◽  
Mouse Brain ◽  
Brain Barrier ◽  
Normal Brain ◽  
Drug Penetration ◽  
Expression Levels ◽  
Transporter Protein ◽  
Blood Brain

Abstract BACKGROUND Mechanistic understanding and quantitative prediction of drug penetration across the human blood-brain barrier (BBB) is critical to rational drug development and treatment for brain cancer especially glioblastoma. However, prediction of drug brain/tumor penetration has been significantly hindered mainly due to the lack of quantitation data on transporter protein expression levels at the human BBB. This study was to determine protein expression levels of major transporters and markers at the BBB of human brain and glioblastoma. METHOD The absolute protein expression levels of major transporters and markers were determined in isolated microvessels of human brain (N=30), glioblastoma (N=47), rat (N=10) and mouse brain (N=10), using liquid chromatography with tandem mass spectrometry (LC-MS/MS) based targeted proteomics. RESULTS In isolated microvessels of 30 human brain specimens, the median protein abundances for ABCB1, ABCG2, GLUT1, GLUT3, LAT1, MCT1, Na/K ATPase, and Claudin-5 were 3.38, 6.21, 54.51, 7.17, 3.42, 5.71, 32.14, and 1.15 fmol/µg protein, respectively. In glioblastoma microvessels, ABCB1, ABCG2, MCT1, GLUT1, Na/K ATPase, and Claudin-5 protein levels were significantly reduced, while LAT1 was increased and GLU1 remained the same. ABCC4, OATP1A2, OATP2B1, and OAT3 were undetectable in isolated microvessels of both human brain and glioblastoma. There was species difference in transporter protein expression levels in isolated microvessels of human, rat and mouse brain. Specifically, rodent BBB expressed significantly higher ABCB1 but similar ABCG2, as compared to human BBB. CONCLUSION The physical and biochemical barriers of the BBB in glioblastomas are largely disrupted, as indicated by the loss or significant reduction in protein expression of the tight junction marker (claudin-5), brain endothelial cell marker (GLUT1), and major efflux transporters (ABCB1 and ABCG2) as compared to normal human BBB. Differential BBB transporter protein expression levels provides mechanistic and quantitative basis for the prediction of heterogeneous drug penetration into human normal brain and glioblastoma.

scholarly journals Transport of ultrasmall gold nanoparticles (2 nm) across the blood–brain barrier in a six-cell brain spheroid model

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Viktoriya Sokolova ◽  
Gehad Mekky ◽  
Selina Beatrice van der Meer ◽  
Michael C. Seeds ◽  
Anthony J. Atala ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Blood Brain Barrier ◽  
Laser Scanning ◽  
Laser Scanning Microscopy ◽  
Brain Barrier ◽  
Confocal Laser ◽  
Hydrodynamic Diameter ◽  
Core Diameter ◽  
Blood Brain

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.

scholarly journals Blood-brain barrier amenable gold nanoparticles biofabrication in aged cell culture medium

2020 ◽  
Vol 8 ◽  
pp. 100072
Author(s):  
F.U. Rehman ◽  
J. Bao ◽  
P. Muhammad ◽  
W. He ◽  
S. Hanif ◽  
...  
Keyword(s):  
Cell Culture ◽  
Gold Nanoparticles ◽  
Blood Brain Barrier ◽  
Culture Medium ◽  
Brain Barrier ◽  
Cell Culture Medium ◽  
Blood Brain ◽  
Aged Cell

scholarly journals Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier Level

2021 ◽  
Vol 22 (7) ◽  
pp. 3742
Author(s):  
Sweilem B. Al Rihani ◽  
Lucy I. Darakjian ◽  
Malavika Deodhar ◽  
Pamela Dow ◽  
Jacques Turgeon ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Drug Transporters ◽  
Neurovascular Unit ◽  
Drug Distribution ◽  
Drug Efficacy ◽  
Brain Barrier ◽  
Protective Function ◽  
Transporter Protein ◽  
Blood Brain ◽  
The Brain

The blood–brain barrier (BBB) is a highly selective and restrictive semipermeable network of cells and blood vessel constituents. All components of the neurovascular unit give to the BBB its crucial and protective function, i.e., to regulate homeostasis in the central nervous system (CNS) by removing substances from the endothelial compartment and supplying the brain with nutrients and other endogenous compounds. Many transporters have been identified that play a role in maintaining BBB integrity and homeostasis. As such, the restrictive nature of the BBB provides an obstacle for drug delivery to the CNS. Nevertheless, according to their physicochemical or pharmacological properties, drugs may reach the CNS by passive diffusion or be subjected to putative influx and/or efflux through BBB membrane transporters, allowing or limiting their distribution to the CNS. Drug transporters functionally expressed on various compartments of the BBB involve numerous proteins from either the ATP-binding cassette (ABC) or the solute carrier (SLC) superfamilies. Pathophysiological stressors, age, and age-associated disorders may alter the expression level and functionality of transporter protein elements that modulate drug distribution and accumulation into the brain, namely, drug efficacy and toxicity. This review focuses and sheds light on the influence of inflammatory conditions and diseases such as Alzheimer’s disease, epilepsy, and stroke on the expression and functionality of the BBB drug transporters, the consequential modulation of drug distribution to the brain, and their impact on drug efficacy and toxicity.

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