Transport of Transferrin Receptor-Targeted Antibodies Through the Blood-Brain Barrier for Drug Delivery to the Brain

Moos, Torben; Gudbergsson, Johann Mar; Johnsen, Kjeld

doi:10.1007/978-3-030-88773-5_17

Cited by 3 publications

(2 citation statements)

References 87 publications

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“…The transport of nanoparticles through BECs appears to depend on the affinity or low avidity of the anti-transferrin receptor antibody. Nanoparticles, therefore, may undergo transport through BECs similar to therapeutically active molecules like enzymes or other proteins directly conjugated to anti-transferrin receptor antibodies [ 73 ] ( Figure 5 ).…”

Section: A Mechanistic Approach To An Understanding Of Trafficking Of...mentioning

confidence: 99%

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: A Mechanistic Approach To An Understanding Of Trafficking Of...mentioning

confidence: 99%

Blood–Brain Barrier Transport of Transferrin Receptor-Targeted Nanoparticles

et al. 2022

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Section: Endothelium To Brain Transportmentioning

confidence: 99%

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

A novel bispecific antibody able to pass the blood-brain barrier and therapeutically engage within the brain

Thomsen

Moos

2022

Med

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Transport of Transferrin Receptor-Targeted Antibodies Through the Blood-Brain Barrier for Drug Delivery to the Brain

Cited by 3 publications

References 87 publications

Blood–Brain Barrier Transport of Transferrin Receptor-Targeted Nanoparticles

Blood–Brain Barrier Transport of Transferrin Receptor-Targeted Nanoparticles

Blood-Brain Barrier Transport of Transferrin-Receptor Targeted Nanoparticles

A novel bispecific antibody able to pass the blood-brain barrier and therapeutically engage within the brain

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