Evidence map›Paper›PMID 34147718›Full record

ArticleBiomaterials2021

Reversible blood-brain barrier opening utilizing the membrane active peptide melittin in vitro and in vivo.

Raleigh M Linville, Alexander Komin, Xiaoyan Lan, Jackson G DeStefano, Chengyan Chu, Guanshu Liu, Piotr Walczak, Kalina Hristova, Peter C Searson

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomaterials, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

21 citing papers in PubMed, 48 citations in OpenAlex.

  1. Review
  2. Review
  3. A SynB1-conjugated antibody cocktail crosses the blood-brain barrier to produce a therapeutic effect on rabies.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  5. Permeability Benchmarking: Guidelines for ComparingJournal of chemical information and modeling · 2025
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  8. Next-generation agents for fluorescence-guided glioblastoma surgery.Bioengineering & translational medicine · 2024
    Article
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  11. Review
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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

9 authors at 2 institutions in 1 country.

Raleigh M LinvilleInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
Alexander KominInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.
Xiaoyan LanDepartment of Diagnostic Radiology & Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Jackson G DeStefanoInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.
Chengyan ChuDepartment of Diagnostic Radiology & Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Guanshu LiuDepartment of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Piotr WalczakDepartment of Diagnostic Radiology & Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Kalina HristovaInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.
Peter C SearsonInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA. Electronic address: searson@jhu.edu.
Johns Hopkins University · USUniversity of Maryland, Baltimore · US

Funding

BIOMEDICAL ENGINEERING TRAINING PROGRAMT32GM007057 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI KANOLD, PATRICK O, KARCHIN, RACHEL · 1985 to 2023
$10.4M
T32: Predoctoral and Postdoctoral Training Program in Nanotechnology for Cancer ResearchT32CA153952 · NCI · JOHNS HOPKINS UNIVERSITY · PI Denis Wirtz · 2015 to 2026
$3.5M
Mechanisms of cerebrovascular barrier dysfunction caused by APP and PSEN1 mutations and amyloid beta exposureR01NS106008 · NINDS · JOHNS HOPKINS UNIVERSITY · PI SEARSON, PETER C · 2019 to 2023
$1.9M
T-32 NIH Postdoctoral Training Program in Nanotechnology for Cancer Medicine NTCMT32CA130840 · NCI · JOHNS HOPKINS UNIVERSITY · PI WIRTZ, DENIS · 2008 to 2012
$1.2M
Two-pronged therapeutic approach for glioblastoma: high dose radiation therapy then repair of radiation-induced brain injuryR01NS102675 · NINDS · JOHNS HOPKINS UNIVERSITY · PI WALCZAK, PIOTR · 2018 to 2019
$511k
Peptides and Transcellular TransportF31NS101875 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KOMIN, ALEXANDER · 2017 to 2019
$80k
NCI NIH HHS T32 CA130840NCI NIH HHS T32 CA153952NIGMS NIH HHS T32 GM007057NINDS NIH HHS F31 NS101875NINDS NIH HHS R01 NS102675NINDS NIH HHS R01 NS106008
6 · The paper itself

Abstract

The blood-brain barrier (BBB) tightly controls entry of molecules and cells into the brain, restricting the delivery of therapeutics. Blood-brain barrier opening (BBBO) utilizes reversible disruption of cell-cell junctions between brain microvascular endothelial cells to enable transient entry into the brain. Here, we demonstrate that melittin, a membrane active peptide present in bee venom, supports transient BBBO. From endothelial and neuronal viability studies, we first identify the accessible concentration range for BBBO. We then use a tissue-engineered model of the human BBB to optimize dosing and elucidate the mechanism of opening. Melittin and other membrane active variants transiently increase paracellular permeability via disruption of cell-cell junctions that result in transient focal leaks. To validate the results from the tissue-engineered model, we then demonstrate that transient BBBO can be reproduced in a mouse model. We identify a minimum clinically effective intra-arterial dose of 3 μM min melittin, which is reversible within one day and neurologically safe. Melittin-induced BBBO represents a novel technology for delivery of therapeutics into the brain.

Indexed as

Blood-Brain BarrierMelittenAnimalsBiological TransportBrainEndothelial CellsMiceMelittenBlood-brain barrierDrug deliveryMelittinPeptideTissue engineering

Identifiers

PMID34147718
PMCPMC8330225
OpenAlexW3167836493

What OpenQuestion holds

Textmetadata
LicenceTDM
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.