Evidence map›Paper›PMID 29570264›Full record

ArticleACS applied materials & interfaces2018

Enzyme Prodrug Therapy Achieves Site-Specific, Personalized Physiological Responses to the Locally Produced Nitric Oxide.

Anna K Winther, Betina Fejerskov, Marja Ter Meer, Najah B S Jensen, Ross Dillion, Jeremy E Schaffer, Rona Chandrawati, Molly M Stevens, Leo J Schultze Kool, Ulf Simonsen and 1 more

Open access · hybridAbstract read
In one paragraph

Article in ACS applied materials & interfaces, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

10 citing papers in PubMed, 37 citations in OpenAlex.

  1. Therapeutic Gases in Biomedicine: Updates on Nitric Oxide and Beyond.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  2. Metal-Organic Frameworks: Unlocking New Frontiers in Cardiovascular Diagnosis and Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  3. Review
  4. Review
  5. Applying Principles of Regenerative Medicine to Vascular Stent Development.Frontiers in bioengineering and biotechnology · 2022
    Review
  6. Nitric Oxide to Fight Viral Infections.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021
    Review
  7. Review
  8. Article
  9. Biotransporting Biocatalytic Reactors toward Therapeutic Nanofactories.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2018
    Article
  10. Combatting implant-associated biofilms through localized drug synthesis.Journal of controlled release : official journal of the Controlled Release Society · 2018
    Article
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

11 authors at 4 institutions in 3 countries.

Anna K Winther
Betina Fejerskov
Marja Ter MeerDepartment of Radiology and Nuclear Medicine 766 , Radboud University Medical Center , Nijmegen 6525 , The Netherlands.
Najah B S Jensen
Ross DillionFort Wayne Metals, Research and Development , Fort Wayne 46809 , Indiana , United States.
Jeremy E SchafferFort Wayne Metals, Research and Development , Fort Wayne 46809 , Indiana , United States.
Rona ChandrawatiDepartment of Materials, Department of Bioengineering, and Institute of Biomedical Engineering , Imperial College London , London SW7 2AZ , U.K.
Molly M StevensDepartment of Materials, Department of Bioengineering, and Institute of Biomedical Engineering , Imperial College London , London SW7 2AZ , U.K.ORCID http://orcid.org/0000-0002-7335-266X
Leo J Schultze KoolDepartment of Radiology and Nuclear Medicine 766 , Radboud University Medical Center , Nijmegen 6525 , The Netherlands.
Ulf Simonsen
Aarhus University · DKFort Wayne Metals (United States)Imperial College London · GBRadboud University Nijmegen · NL

Funding

European Research Council 616417European Research Council 617336Wellcome Trust 098411
6 · The paper itself

Abstract

Nitric oxide (NO) is a highly potent but short-lived endogenous radical with a wide spectrum of physiological activities. In this work, we developed an enzymatic approach to the site-specific synthesis of NO mediated by biocatalytic surface coatings. Multilayered polyelectrolyte films were optimized as host compartments for the immobilized β-galactosidase (β-Gal) enzyme through a screen of eight polycations and eight polyanions. The lead composition was used to achieve localized production of NO through the addition of β-Gal-NONOate, a prodrug that releases NO following enzymatic bioconversion. The resulting coatings afforded physiologically relevant flux of NO matching that of the healthy human endothelium. The antiproliferative effect due to the synthesized NO in cell culture was site-specific: within a multiwell dish with freely shared media and nutrients, a 10-fold inhibition of cell growth was achieved on top of the biocatalytic coatings compared to the immediately adjacent enzyme-free microwells. The physiological effect of NO produced via the enzyme prodrug therapy was validated ex vivo in isolated arteries through the measurement of vasodilation. Biocatalytic coatings were deposited on wires produced using alloys used in clinical practice and successfully mediated a NONOate concentration-dependent vasodilation in the small arteries of rats. The results of this study present an exciting opportunity to manufacture implantable biomaterials with physiological responses controlled to the desired level for personalized treatment.

Indexed as

Animalsbeta-GalactosidaseEndothelium, VascularEnzyme InhibitorsEnzymes, ImmobilizedHumansNitric OxideProdrugsRatsVasodilationbeta-GalactosidaseEnzyme InhibitorsEnzymes, ImmobilizedNitric OxideProdrugsbiocatalytic coatingenzyme-prodrug therapygalactosidasenitric oxidepolyelectrolyte multilayersstentvasodilatation

Identifiers

PMID29570264
PMCPMC5887086
OpenAlexW2790827215

What OpenQuestion holds

Textmetadata
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.