The Significance of the Choroid Plexus for Cerebral Iron Homeostasis

Routhe, Lisa Juul; Thomsen, Maj Schneider; Moos, Torben

doi:10.1007/978-1-0716-0536-3_5

Cited by 4 publications

(7 citation statements)

References 110 publications

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“…From a quantitative drug delivery perspective, passaging across the BBB is by far the most important as the brain microvasculature has a surface area thousand-fold higher than that of the choroid plexus. This allows drugs to enter the entire brain while transport across the blood–CSF barrier is restricted to the ventricular system [ 2 , 3 , 15 ].…”

Section: Passaging Of Large Molecules Through the Blood–brain And Blo...mentioning

confidence: 99%

“…Returning to the attempts to enable transport through the choroid plexus, it should not be overlooked that there is strong morphological and physiological evidence for vesicular transport by transcytosis through this epithelium. Ultrastructurally, tracer studies using peroxidases demonstrate that the choroid plexus epithelium can take up large molecules like horseradish peroxidase (HRP) with transfer from the basolateral to the luminal side eventually leading to release into the ventricles [ 15 , 34 , 35 ]. The choroid plexus, contrary to the brain endothelium, also contains vesicular structures with albumin, IgG, and transferrin.…”

Section: The Transferrin Receptor As Target For Drug Deliverymentioning

confidence: 99%

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Blood–Brain Barrier Transport of Transferrin Receptor-Targeted Nanoparticles

et al. 2022

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The blood–brain barrier (BBB), built by brain endothelial cells (BECs), is impermeable to biologics. Liposomes and other nanoparticles are good candidates for the delivery of biologics across the BECs, as they can encapsulate numerous molecules of interest in an omnipotent manner. The liposomes need attachment of a targeting molecule, as BECs unfortunately are virtually incapable of uptake of non-targeted liposomes from the circulation. Experiments of independent research groups have qualified antibodies targeting the transferrin receptor as superior for targeted delivery of nanoparticles to BECs. Functionalization of nanoparticles via conjugation with anti-transferrin receptor antibodies leads to nanoparticle uptake by endothelial cells of both brain capillaries and post-capillary venules. Reducing the density of transferrin receptor-targeted antibodies conjugated to liposomes limits uptake in BECs. Opposing the transport of nanoparticles conjugated to high-affine anti-transferrin receptor antibodies, lowering the affinity of the targeting antibodies or implementing monovalent antibodies increase uptake by BECs and allows for further transport across the BBB. The novel demonstration of transport of targeted liposomes in post-capillary venules from blood to the brain is interesting and clearly warrants further mechanistic pursuit. The recent evidence for passing targeted nanoparticles through the BBB shows great promise for future drug delivery of biologics to the brain.

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Section: Passaging Of Large Molecules Through the Blood–brain And Blo...mentioning

confidence: 99%

Section: The Transferrin Receptor As Target For Drug Deliverymentioning

confidence: 99%

Blood–Brain Barrier Transport of Transferrin Receptor-Targeted Nanoparticles

et al. 2022

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“…The blood-CSF barrier is formed by choroid plexus epithelial cells also connected by tight junctions, but opposed to the BBB, the capillaries of the blood-CSF barrier are leaky, meaning that solutes of the plasma diffuse into the extracellular space of the choroid plexus where the epithelial cells selectively transport molecules to the CSF [2,3,14] From a quantitative drug delivery perspective, passaging across the BBB is by far the most important as the brain microvasculature has a surface area thousand-fold higher than that of the choroid plexus. This allow drugs to enter the entire brain while transport across the blood-CSF barrier is restricted to the ventricular system [2,3,15].…”

Section: Passaging Of Large Molecules Through the Blood-brain And Blo...mentioning

confidence: 99%

“…Transport of this antibody through BECs is enabled by the detachment of the antibody from the transferrin receptor in late endosomes, which enables this antibody to undergo transport into the brain. [Modified from [15]] specific binding protein for transferrin, the transferrin receptor (a.k.a. transferrin receptor 1), was identified on BECs [18].…”

Section: The Transferrin Receptor As Target For Drug Deliverymentioning

confidence: 99%

“…This is corroborated by the concentration of these proteins being many folds higher in the ventricular CSF compared to the interstitial fluid of the brain in the CSF [c.f. [15]]. The transport of large plasma proteins could theoretically qualify the blood-CSF barrier as a feasible route for nanoparticles to enter the brain.…”

Section: The Transferrin Receptor As Target For Drug Deliverymentioning

confidence: 99%

See 1 more Smart Citation

Blood-Brain Barrier Transport of Transferrin-Receptor Targeted Nanoparticles

Thomsen¹,

Johnsen²,

Kucharz³

et al. 2022

Preprint

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The blood-brain barrier (BBB), built by brain endothelial cells (BECs), is impermeable to biologics. Liposomes and other nanoparticles are good candidates for delivery of biologics across the BECs, as they can encapsulate numerous molecules of interest in an omnipotent manner. The liposomes need attachment of a targeting molecule, as BECs unfortunately are virtually incapable of uptake of non-targeted liposomes from the circulation. Experiments of independent research groups have qualified antibodies targeting the transferrin receptor as superior for targeted delivery of nanoparticles to BECs. Functionalization of nanoparticles via conjugation with anti-transferrin receptor antibodies leads to nanoparticle uptake by endothelial cells of both brain capillaries and post-capillary venules. Reducing the density of transferrin receptor-targeted antibodies conjugated to liposomes limits uptake in BECs. Opposing the transport of nanoparticles conjugated to high-affine anti-transferrin receptor antibodies, lowering the affinity of the targeting antibodies or implementing monovalent antibodies increase uptake by BECs and allows for further transport across the BBB. The novel demonstration of transport of targeted liposomes in post-capillary venules from blood to the brain is interesting and clearly warrants further mechanistic pursuit. The recent evidence for passing targeted nanoparticles through the BBB shows great promise for future drug delivery of biologics to the brain.

show abstract