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Involvement of the low‐density lipoprotein receptor‐related protein in the transcytosis of the brain delivery vector Angiopep‐2
Abstract
The blood–brain barrier (BBB) restricts the entry of proteins as well as potential drugs to cerebral tissues. We previously reported that a family of Kunitz domain‐derived peptides called Angiopeps can be used as a drug delivery system for the brain. Here, we further characterize the transcytosis ability of these peptides using an in vitro model of the BBB and in situ brain perfusion. These peptides, and in particular Angiopep‐2, exhibited higher transcytosis capacity and parenchymal accumulation than do transferrin, lactoferrin, and avidin. Angiopep‐2 transport and accumulation in brain endothelial cells were unaffected by the P‐glycoprotein inhibitor, cyclosporin A, indicating that this peptide is not a substrate for the efflux pump P‐glycoprotein. However, competition studies show that activated α 2 ‐macroglobulin, a specific ligand for the low‐density lipoprotein receptor‐related protein‐1 (LRP1) and Angiopep‐2 can share the same receptor. In addition, LRP1 was detected in glioblastomas and brain metastases from lung and skin cancers. Fluorescent microscopy also revealed that Alexa488‐Angiopep‐2 co‐localized with LRP1 in brain endothelial cell monolayers. Overall, these results suggest that Angiopep‐2 transport across the BBB is, in part, mediated by LRP1.
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Some exchangeable apolipoproteins (ApoA1 and ApoE) can cross the blood-brain barrier via receptor-mediated transcytosis.
“Some of those exchangeable apolipoproteins (ApoA1 and ApoE) can cross the blood-brain barrier (BBB) via receptor-mediated transcytosis18–21”
From Brain-targeted drug delivery by manipulating protein corona functions (2019) · cites this paper as [21]
Citations
Cites
Astrocyte-endothelial interactions at the blood-brain barrier
Abbott, N. J., Rönnbäck, L., & Hansson, E. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1824 · Cited by 5,595
Yamamoto, M., Ikeda, K., Ohshima, K., Tsugu, H., Kimura, H., & Tomonaga, M. (1998) · Brain Tumor Pathology · doi:10.1007/bf02482097 · Cited by 25
Flagged first, then by citations
Research works printed but not linked: 42
- El‐Bacha R. S., 1999, Drug metabolizing enzymes in cerebrovascular endothelial cells afford a metabolic protection to the brain, Cell. Mol. Biol. (Noisy-le-grand), 45, 15
- 10.1381/096089206776944959 · DOI
- 10.1124/jpet.102.036129 · DOI
- 10.1016/0005-2736(94)00239-L · DOI
- 10.2174/1381612043384844 · DOI
- 10.1016/j.pharmthera.2004.08.001 · DOI · Paper page
- 10.1016/S0169-409X(00)00139-3 · DOI
- 10.1146/annurev.pharmtox.47.120505.105237 · DOI
- 10.1186/1750-1326-1-8 · DOI · Paper page
- 10.1023/A:1011080418027 · DOI
- 10.1074/jbc.M513645200 · DOI
- 10.1097/00004647-200002000-00020 · DOI
- 10.1042/bj2760745 · DOI
- 10.1111/j.1471-4159.1990.tb01236.x · DOI
- 10.1111/j.1471-4159.1992.tb10055.x · DOI
- 10.1046/j.1471-4159.2002.01201.x · DOI
- 10.1124/jpet.107.131318 · DOI
- 10.1016/j.mcn.2004.03.005 · DOI
- 10.1074/jbc.274.11.7011 · DOI
- 10.1002/jnr.490180206 · DOI
- 10.1111/j.1749-6632.1994.tb44318.x · DOI
- 10.1146/annurev.nutr.19.1.141 · DOI
- 10.3109/10611860008997917 · DOI
- 10.1046/j.1471-4159.2003.02081.x · DOI
- 10.1038/sj.ijo.0802206 · DOI
- 10.1016/0092-8674(95)90320-8 · DOI · Paper page
- 10.1016/j.pharmthera.2007.05.009 · DOI
- 10.1172/JCI118176 · DOI
- 10.1124/jpet.103.051821 · DOI
- 10.1002/cncr.21301 · DOI
- 10.3109/13550289909021285 · DOI
- 10.1254/jjp.87.97 · DOI
- 10.1602/neurorx.2.1.3 · DOI · Paper page
- 10.1016/0014-5793(91)80996-G · DOI
- Pardridge W. M., 1991, Selective transport of an anti‐transferrin receptor antibody through the blood–brain barrier in vivo, J. Pharmacol. Exp. Ther., 259, 66
- Penichet M. L., 1999, An antibody‐avidin fusion protein specific for the transferrin receptor serves as a delivery vehicle for effective brain targeting: initial applications in anti‐HIV antisense drug delivery to the brain, J. Immunol., 163, 4421, 10.4049/jimmunol.163.8.4421 · DOI
- 10.1038/bjp.2008.260 · DOI
- 10.1002/jcp.1041590114 · DOI
- 10.1016/S0169-409X(98)00084-2 · DOI · Paper page
- Yamamoto M., 1997, Increased expression of low density lipoprotein receptor‐related protein/alpha2‐macroglobulin receptor in human malignant astrocytomas, Cancer Res., 57, 2799
- 10.2337/diabetes.48.5.1026 · DOI · Paper page
- 10.1124/jpet.104.082974 · DOI
Cited by
Sorted by citations
Nicolas, J., Mura, S., Brambilla, D., Mackiewicz, N., & Couvreur, P. (2013) · Chem. Soc. Rev. · doi:10.1039/c2cs35265f · Cited by 1,270
Strategies for delivering therapeutics across the blood–brain barrier
Terstappen, G. C., Meyer, A. H., Bell, R. D., & Zhang, W. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00139-y · Cited by 1,138
Nanotechnological advances for the delivery of cns therapeutics.
Wong, H. L., Wu, X. Y., & Bendayan, R. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2011.10.007 · Cited by 488
Targeting Receptor-Mediated Transport for Delivery of Biologics Across the Blood-Brain Barrier
Lajoie, J. M., & Shusta, E. V. (2015) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010814-124852 · Cited by 399
Brain-targeted drug delivery by manipulating protein corona functions
Zhang, Z., Guan, J., Jiang, Z., Yang, Y., Liu, J., Hua, W., Mao, Y., Li, C., Lu, W., Qian, J., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11593-z · Cited by 334
Zlokovic, B. V., Deane, R., Sagare, A. P., Bell, R. D., & Winkler, E. A. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.07002.x · Cited by 261
Neurovascular Dysfunction and Faulty Amyloid -Peptide Clearance in Alzheimer Disease
Sagare, A. P., Bell, R. D., & Zlokovic, B. V. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a011452 · Cited by 251
Georgieva, J., Hoekstra, D., & Zuhorn, I. (2014) · Pharmaceutics · doi:10.3390/pharmaceutics6040557 · Cited by 211
Nanotechnology—novel therapeutics for CNS disorders
Srikanth, M., & Kessler, J. A. (2012) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.76 · Cited by 198
Phase I Study of GRN1005 in Recurrent Malignant Glioma
Drappatz, J., Brenner, A., Wong, E. T., Eichler, A., Schiff, D., Groves, M. D., Mikkelsen, T., Rosenfeld, S., Sarantopoulos, J., Meyers, C. A., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2481 · Cited by 190
Self-citationHeat shock protein–based therapy as a potential candidate for treating the sphingolipidoses
Kirkegaard, T., Gray, J., Priestman, D. A., Wallom, K.-L., Atkins, J., Olsen, O. D., Klein, A., Drndarski, S., Petersen, N. H. T., Ingemann, L., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad9823 · Cited by 173
Peptide therapeutics for CNS indications
McGonigle, P. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.10.014 · Cited by 95
Zhang, X., He, T., Chai, Z., Samulski, R. J., & Li, C. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.05.041 · Cited by 65
Ding, L., Kshirsagar, P., Agrawal, P., & Murry, D. J. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17060706 · Cited by 62
Ligand conjugation: An emerging platform for enhanced brain drug delivery
Nabi, B., Rehman, S., Khan, S., Baboota, S., & Ali, J. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2018.08.003 · Cited by 44
Israel, L. L., Galstyan, A., Cox, A., Shatalova, E. S., Sun, T., Rashid, M.-H., Grodzinski, Z., Chiechi, A., Fuchs, D.-T., Patil, R., et al. (2022) · ACS Nano · doi:10.1021/acsnano.1c10034 · Cited by 41
Nájera-Maldonado, L., Parra-González, M., Peralta-Cuevas, E., Gutierrez-Onofre, A. J., Garcia-Atutxa, I., & Villanueva-Flores, F. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17091169 · Cited by 40
Short Peptide-Mediated Brain-Targeted Drug Delivery with Enhanced Immunocompatibility
Guan, J., Jiang, Z., Wang, M., Liu, Y., Liu, J., Yang, Y., Ding, T., Lu, W., Gao, C., Qian, J., et al. (2019) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.8b01216 · Cited by 34
Kohman, R. E., Kunjapur, A. M., Hysolli, E., Wang, Y., & Church, G. M. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201707976 · Cited by 33
Mazura, A. D., & Pietrzik, C. U. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15041268 · Cited by 9
Main methods and tools for peptide development based on protein-protein interactions (PPIs)
Baeza, J., Bedoya, M., Cruz, P., Ojeda, P., Adasme-Carreño, F., Cerda, O., & González, W. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.151623 · Cited by 8
Pratt, J., Haidara, K., & Annabi, B. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232214214 · Cited by 8
Metadata
- Authors
- Demeule, M., Currie, J., Bertrand, Y., Ché, C., Nguyen, T., Régina, A., Gabathuler, R., Castaigne, J., & Béliveau, R.
- Affiliations
- Angiochem (Canada) (CA)
- Université du Québec à Montréal (CA)
- Corresponding author
- Gabathuler, Reinhard
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2008-08
- Volume
- 106
- Issue
- 4
- Pages
- 1534-1544
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1995195889
- Cited by
- 557
- References
- 2
- Citations by year
- 2026: 28 · 2025: 27 · 2024: 35 · 2023: 40 · 2022: 46 · 2021: 46 · 2020: 50 · 2019: 25 · 2018: 41 · 2017: 30 · 2016: 32 · 2015: 26 · 2014: 29 · 2013: 24 · 2012: 28
- FWCI
- 10.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Sciences and Engineering Research Council of Canada
- National Research Council Canada
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- Angiopep-2, LRP1, blood-brain barrier, transcytosis, brain drug delivery, alpha2-macroglobulin, P-glycoprotein, brain endothelial cells, glioblastoma, brain metastases, receptor-mediated transport
- MeSH terms
- Animals, Blood-Brain Barrier, Brain, Cattle, Cells, Cultured, Genetic Vectors, Humans, Oligopeptides, Peptide Fragments, Peptides, Cyclic, Somatostatin, Drug Delivery Systems, Protein Transport, Low Density Lipoprotein Receptor-Related Protein-1, Cell Line, Tumor, Rats
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