TY - JOUR

T1 - Blood-Brain Barrier Transport of Transferrin Receptor-Targeted Nanoparticles

AU - Thomsen, Maj Schneider

AU - Johnsen, Kasper Bendix

AU - Kucharz, Krzysztof

AU - Lauritzen, Martin

AU - Moos, Torben

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - antibody

KW - blood-brain barrier

KW - endosomal

KW - liposome

KW - nanoparticle

KW - targeting

KW - transferrin

KW - CAPILLARY ENDOTHELIAL-CELLS

KW - MEDIATED TRANSCYTOSIS

KW - ANTIBODY-AFFINITY

KW - DRUG TRANSPORT

KW - IRON

KW - DELIVERY

KW - RAT

KW - EXPRESSION

KW - LIPOSOMES

KW - ALBUMIN

U2 - 10.3390/pharmaceutics14102237

DO - 10.3390/pharmaceutics14102237

M3 - Review

C2 - 36297671

VL - 14

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 10

M1 - 2237

ER -