Differential expression of receptors mediating receptor-mediated transcytosis (RMT) in brain microvessels, brain parenchyma and peripheral tissues of the mouse and the human

Fluids and Barriers of the CNS, Год журнала: 2020, Номер 17(1)

Опубликована: Июль 22, 2020

Abstract Receptor-mediated transcytosis (RMT) is a principal pathway for transport of macromolecules essential brain function across the blood–brain barrier (BBB). Antibodies or peptide ligands which bind RMT receptors are often co-opted delivery biotherapeutics. Constitutively recycling transferrin receptor (TfR) prototype utilized to shuttle therapeutic cargos BBB. Several other BBB-expressed have been shown mediate antibodies protein including insulin (INSR) and insulin-like growth factor-1 (IGF1R), lipid transporters LRP1, LDLR, LRP8 TMEM30A, solute carrier family transporter SLC3A2/CD98hc leptin (LEPR). In this study, we analyzed expression patterns genes encoding in isolated microvessels, parenchyma peripheral organs mouse human using RNA-seq approach. IGF1R, INSR were highly enriched microvessels compared tissues. only was either lung. The levels SLC2A1, TFRC significantly higher microvessels. these by Western blot immunofluorescent staining correlated with their transcript abundance. This study provides molecular transcriptomics map key tissues, important translational studies biodistribution, efficacy safety developed against receptors.

Язык: Английский

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Mechanisms of Pathogen Invasion into the Central Nervous System

Neuron, Год журнала: 2019, Номер 103(5), С. 771 - 783

Опубликована: Сен. 1, 2019

Язык: Английский

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Brain uptake pharmacokinetics of incretin receptor agonists showing promise as Alzheimer’s and Parkinson’s disease therapeutics

Biochemical Pharmacology, Год журнала: 2020, Номер 180, С. 114187 - 114187

Опубликована: Авг. 2, 2020

Язык: Английский

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Systematic Evaluation of Transferrin-Modified Porous Silicon Nanoparticles for Targeted Delivery of Doxorubicin to Glioblastoma

ACS Applied Materials & Interfaces, Год журнала: 2019, Номер 11(37), С. 33637 - 33649

Опубликована: Авг. 21, 2019

There is a dire need to develop more effective therapeutics combat brain cancer such as glioblastoma multiforme (GBM). An ideal treatment expected target deliver chemotherapeutics glioma cells across the blood-brain barrier (BBB). The overexpression of transferrin (Tf) receptor (TfR) on BBB and GBM cell surfaces but not surrounding renders TfR promising target. While porous silicon nanoparticles (pSiNPs) have been intensely studied delivery vehicle due their high biocompatibility, degradability, drug-loading capacity, potential drugs with (Tf)-functionalized pSiNPs remains unaddressed. Here, we developed systematically evaluated Tf-functionalized (Tf@pSiNPs) glioma-targeted drug system. These showed excellent colloidal stability had low toxicity profile. As compared nontargeted pSiNPs, Tf@pSiNPs were selective BBB-forming efficiently internalized through clathrin receptor-mediated endocytosis. anticancer doxorubicin (Dox) was effectively loaded (8.8 wt %) released from in pH-responsive manner over 24 h. Furthermore, results demonstrate that Dox delivered by induced significantly enhanced cytotoxicity an vitro monolayer free Dox. Overall, offer toolbox for enabling targeted therapy treat GBM.

Язык: Английский

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Activation of endothelial Wnt/β-catenin signaling by protective astrocytes repairs BBB damage in ischemic stroke

Progress in Neurobiology, Год журнала: 2020, Номер 199, С. 101963 - 101963

Опубликована: Ноя. 26, 2020

Язык: Английский

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