Blood–Brain Barrier Transport of Therapeutics via Receptor-Mediation
Open accessAbstract
Drug delivery to the brain is hindered by the presence of the blood-brain barrier (BBB). Although the BBB restricts the passage of many substances, it is actually selectively permeable to nutrients necessary for healthy brain function. To accomplish the task of nutrient transport, the brain endothelium is endowed with a diverse collection of molecular transport systems. One such class of transport system, known as a receptor-mediated transcytosis (RMT), employs the vesicular trafficking machinery of the endothelium to transport substrates between blood and brain. If appropriately targeted, RMT systems can also be used to shuttle a wide range of therapeutics into the brain in a noninvasive manner. Over the last decade, there have been significant developments in the arena of RMT-based brain drug transport, and this review will focus on those approaches that have been validated in an in vivo setting.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Tau pathology is linked to cognitive decline, may progress more rapidly than Aβ accumulation, and correlates with neuroinflammation, making it a valuable prognostic marker.
“Numerous studies have linked tau pathology to cognitive decline, with some evidence suggesting it progresses more rapidly than Aβ accumulation and correlates with neuroinflammation, making it a valuable prognostic marker [20, 25–28].”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [25]
The blood-brain barrier is a major obstacle to delivering many drugs to the brain.
“The BBB is a major obstacle to delivering many drugs to the brain, highlighting the importance of developing NP systems capable of traversing this barrier to advance AD treatments [25].”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [25]
Nanoparticles offer significant potential as a therapeutic approach for Alzheimer's disease, particularly in overcoming challenges posed by the blood-brain barrier.
“NPs offer significant potential as a therapeutic approach for AD, particularly in overcoming challenges posed by the BBB.”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [25]
Cites
Tyrosine Hydroxylase and Parkinson’s Disease
Haavik, J., & Toska, K. (1998) · Molecular Neurobiology · doi:10.1007/bf02741387 · Cited by 263 · see citing works
Insulin and insulin receptors in rodent brain
Havrankova, J., Brownstein, M., & Roth, J. (1981) · Diabetologia · doi:10.1007/bf00254492 · Cited by 201 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Crossing the blood-brain barrier with nanoparticles
Zhou, Y., Peng, Z., Seven, E. S., & Leblanc, R. M. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2017.12.015 · Cited by 837 · see citing works
Boosting Brain Uptake of a Therapeutic Antibody by Reducing Its Affinity for a Transcytosis Target
Yu, Y. J., Zhang, Y., Kenrick, M., Hoyte, K., Luk, W., Lu, Y., Atwal, J., Elliott, J. M., Prabhu, S., Watts, R. J., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002230 · Cited by 794 · see citing works
The blood-brain barrier in aging and neurodegeneration
Knox, E. G., Aburto, M. R., Clarke, G., Cryan, J. F., & O’Driscoll, C. M. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01511-z · Cited by 738 · see citing works
The blood-brain barrier: Physiology and strategies for drug delivery
Pandit, R., Chen, L., & Götz, J. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2019.11.009 · Cited by 651 · see citing works
The biology of brain metastases—translation to new therapies
Eichler, A. F., Chung, E., Kodack, D. P., Loeffler, J. S., Fukumura, D., & Jain, R. K. (2011) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2011.58 · Cited by 567 · see citing works
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 · see citing works
Self-citationEvolving Drug Delivery Strategies to Overcome the Blood Brain Barrier
S. Hersh, D., S. Wadajkar, A., B. Roberts, N., G. Perez, J., P. Connolly, N., Frenkel, V., A. Winkles, J., F. Woodworth, G., & J. Kim, A. (2016) · Current Pharmaceutical Design · doi:10.2174/1381612822666151221150733 · Cited by 387 · see citing works
Therapeutic bispecific antibodies cross the blood-brain barrier in nonhuman primates
Yu, Y. J., Atwal, J. K., Zhang, Y., Tong, R. K., Wildsmith, K. R., Tan, C., Bien-Ly, N., Hersom, M., Maloney, J. A., Meilandt, W. J., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009835 · Cited by 371 · see citing works
Solid Lipid Nanoparticles (SLNs): An Advanced Drug Delivery System Targeting Brain through BBB
Satapathy, M. K., Yen, T.-L., Jan, J.-S., Tang, R.-D., Wang, J.-Y., Taliyan, R., & Yang, C.-H. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13081183 · Cited by 318 · see citing works
Neuronal and vascular interactions
Andreone, B. J., Lacoste, B., & Gu, C. (2015) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071714-033835 · Cited by 256 · see citing works
Ullman, J. C., Arguello, A., Getz, J. A., Bhalla, A., Mahon, C. S., Wang, J., Giese, T., Bedard, C., Kim, D. J., Blumenfeld, J. R., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aay1163 · Cited by 205 · see citing works
Human pluripotent stem cell–derived brain pericyte–like cells induce blood-brain barrier properties
Stebbins, M. J., Gastfriend, B. D., Canfield, S. G., Lee, M.-S., Richards, D., Faubion, M. G., Li, W.-J., Daneman, R., Palecek, S. P., & Shusta, E. V. (2019) · Science Advances · doi:10.1126/sciadv.aau7375 · Cited by 195 · see citing works
Self-citationLipid nanoparticle-mediated drug delivery to the brain
Khare, P., Edgecomb, S. X., Hamadani, C. M., Tanner, E. E. L., & S Manickam, D. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.114861 · Cited by 187 · see citing works
Xiao, W., Wang, Y., Zhang, H., Liu, Y., Xie, R., He, X., Zhou, Y., Liang, L., & Gao, H. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.120888 · Cited by 174 · see citing works
Poudel, P., & Park, S. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14040835 · Cited by 124 · see citing works
Targeting receptor-ligand chemistry for drug delivery across blood-brain barrier in brain diseases
Anthony, D. P., Hegde, M., Shetty, S. S., Rafic, T., Mutalik, S., & Rao, B. S. S. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119326 · Cited by 110 · see citing works
Zhang, X., He, T., Chai, Z., Samulski, R. J., & Li, C. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.05.041 · Cited by 65 · see citing works
Ding, L., Kshirsagar, P., Agrawal, P., & Murry, D. J. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17060706 · Cited by 62 · see citing works
Gadkar, K., Yadav, D. B., Zuchero, J. Y., Couch, J. A., Kanodia, J., Kenrick, M. K., Atwal, J. K., Dennis, M. S., Prabhu, S., Watts, R. J., et al. (2016) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2016.01.009 · Cited by 52 · see citing works
Kochman, U., Sitka, H., Kuźniar, J., Czaja, M., Kozubek, P., Beszłej, J. A., & Leszek, J. (2026) · Molecular Neurobiology · doi:10.1007/s12035-025-05417-z · Cited by 60 · see citing works
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 · see citing works
Nanocarriers as cns drug delivery systems for enhanced neuroprotection
Ozkizilcik, A., Davidson, P., Turgut, H., Sharma, H. S., Sharma, A., & Tian, Z. R. (2017) · Drug and Gene Delivery to the Central Nervous System for Neuroprotection · doi:10.1007/978-3-319-57696-1_2 · Cited by 10 · see citing works
- Authors
- Jones, A. R., & Shusta, E. V.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Shusta, Eric V.
- ORCID
- Shusta, Eric V.
- Venue
- Pharmaceutical Research
- Published
- 2007-07-10
- Volume
- 24
- Issue
- 9
- Pages
- 1759-1771
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- PMC
- PMC2685177
- OpenAlex
- W2144232916
- Cited by
- 549
- References
- 2
- Citations by year
- 2026: 30 · 2025: 42 · 2024: 40 · 2023: 33 · 2022: 42 · 2021: 27 · 2020: 38 · 2019: 22 · 2018: 33 · 2017: 40 · 2016: 26 · 2015: 31 · 2014: 29 · 2013: 34 · 2012: 18
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Pharmaceutical Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS052649, NS052649.)
- 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
- blood-brain barrier, receptor-mediated transcytosis, brain drug delivery, brain endothelium, vesicle trafficking, nutrient transport, blood-brain barrier permeability
- MeSH terms
- Animals, Bacterial Proteins, Biological Transport, Blood-Brain Barrier, Brain, Humans, Receptors, Cell Surface, Receptor, Insulin, Receptors, Transferrin, Drug Delivery Systems, Low Density Lipoprotein Receptor-Related Protein-1, Low Density Lipoprotein Receptor-Related Protein-2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
