Blood–Brain Barrier Transport of Transferrin Receptor-Targeted Nanoparticles
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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/14/10/2237 |
| _version_ | 1797470262531194880 |
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| author | Maj Schneider Thomsen Kasper Bendix Johnsen Krzysztof Kucharz Martin Lauritzen Torben Moos |
| author_facet | Maj Schneider Thomsen Kasper Bendix Johnsen Krzysztof Kucharz Martin Lauritzen Torben Moos |
| author_sort | Maj Schneider Thomsen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T19:34:12Z |
| format | Article |
| id | doaj.art-032e5a6f16ef45dc9d4dac4f340b4596 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T19:34:12Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-032e5a6f16ef45dc9d4dac4f340b45962023-11-24T01:58:46ZengMDPI AGPharmaceutics1999-49232022-10-011410223710.3390/pharmaceutics14102237Blood–Brain Barrier Transport of Transferrin Receptor-Targeted NanoparticlesMaj Schneider Thomsen0Kasper Bendix Johnsen1Krzysztof Kucharz2Martin Lauritzen3Torben Moos4Neurobiology Research and Drug Delivery, Department of Health Science and Technology, Aalborg University, 9220 Aalborg, DenmarkNeurobiology Research and Drug Delivery, Department of Health Science and Technology, Aalborg University, 9220 Aalborg, DenmarkDepartment of Neuroscience, Faculty of Health Sciences, University of Copenhagen, 2100 Copenhagen, DenmarkDepartment of Neuroscience, Faculty of Health Sciences, University of Copenhagen, 2100 Copenhagen, DenmarkNeurobiology Research and Drug Delivery, Department of Health Science and Technology, Aalborg University, 9220 Aalborg, DenmarkThe 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.https://www.mdpi.com/1999-4923/14/10/2237antibodyblood–brain barrierendosomalliposomenanoparticletargeting |
| spellingShingle | Maj Schneider Thomsen Kasper Bendix Johnsen Krzysztof Kucharz Martin Lauritzen Torben Moos Blood–Brain Barrier Transport of Transferrin Receptor-Targeted Nanoparticles Pharmaceutics antibody blood–brain barrier endosomal liposome nanoparticle targeting |
| title | Blood–Brain Barrier Transport of Transferrin Receptor-Targeted Nanoparticles |
| title_full | Blood–Brain Barrier Transport of Transferrin Receptor-Targeted Nanoparticles |
| title_fullStr | Blood–Brain Barrier Transport of Transferrin Receptor-Targeted Nanoparticles |
| title_full_unstemmed | Blood–Brain Barrier Transport of Transferrin Receptor-Targeted Nanoparticles |
| title_short | Blood–Brain Barrier Transport of Transferrin Receptor-Targeted Nanoparticles |
| title_sort | blood brain barrier transport of transferrin receptor targeted nanoparticles |
| topic | antibody blood–brain barrier endosomal liposome nanoparticle targeting |
| url | https://www.mdpi.com/1999-4923/14/10/2237 |
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