Evidence map›Paper›PMID 34226541›Full record

ArticleNature communications2021

Post-capillary venules are the key locus for transcytosis-mediated brain delivery of therapeutic nanoparticles.

Krzysztof Kucharz, Kasper Kristensen, Kasper Bendix Johnsen, Mette Aagaard Lund, Micael Lønstrup, Torben Moos, Thomas Lars Andresen, Martin Johannes Lauritzen

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
7.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

67 citing papers in PubMed, 116 citations in OpenAlex.

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  14. Development of the blood-brain barrier.Development (Cambridge, England) · 2026
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  16. Intravenous lipid-siRNA conjugate mediates gene silencing at the blood-brain barrier and blood-CSF barrier.Journal of controlled release : official journal of the Controlled Release Society · 2025
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7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Krzysztof Kucharz *Department of Neuroscience, Faculty of Health Sciences, University of Copenhagen, Copenhagen N, Denmark. kucharz@sund.ku.dk.ORCID http://orcid.org/0000-0002-6852-5300
Kasper Kristensen *Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.ORCID http://orcid.org/0000-0003-3596-4056
Kasper Bendix Johnsen *Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
Mette Aagaard LundDepartment of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
Micael LønstrupDepartment of Neuroscience, Faculty of Health Sciences, University of Copenhagen, Copenhagen N, Denmark.ORCID http://orcid.org/0000-0003-4302-7978
Torben MoosDepartment of Health Science and Technology, Aalborg University, Aalborg Ø, Denmark.
Thomas Lars AndresenDepartment of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
Martin Johannes LauritzenDepartment of Neuroscience, Faculty of Health Sciences, University of Copenhagen, Copenhagen N, Denmark. mlauritz@sund.ku.dk.
Technical University of Denmark · DKUniversity of Copenhagen · DKAalborg University · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Effective treatments of neurodegenerative diseases require drugs to be actively transported across the blood-brain barrier (BBB). However, nanoparticle drug carriers explored for this purpose show negligible brain uptake, and the lack of basic understanding of nanoparticle-BBB interactions underlies many translational failures. Here, using two-photon microscopy in mice, we characterize the receptor-mediated transcytosis of nanoparticles at all steps of delivery to the brain in vivo. We show that transferrin receptor-targeted liposome nanoparticles are sequestered by the endothelium at capillaries and venules, but not at arterioles. The nanoparticles move unobstructed within endothelium, but transcytosis-mediated brain entry occurs mainly at post-capillary venules, and is negligible in capillaries. The vascular location of nanoparticle brain entry corresponds to the presence of perivascular space, which facilitates nanoparticle movement after transcytosis. Thus, post-capillary venules are the point-of-least resistance at the BBB, and compared to capillaries, provide a more feasible route for nanoparticle drug carriers into the brain.

Indexed as

Drug CarriersAnimalsArteriolesBiological TransportBlood-Brain BarrierBrainCapillariesEndotheliumKineticsLiposomesMiceNanoparticlesReceptors, TransferrinTranscytosisVenulesDrug CarriersLiposomesReceptors, Transferrin

Identifiers

PMID34226541
PMCPMC8257611
OpenAlexW3182913217

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.