Evidence map›Paper›PMID 27382168›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

pH-degradable imidazoquinoline-ligated nanogels for lymph node-focused immune activation.

Lutz Nuhn, Nane Vanparijs, Ans De Beuckelaer, Lien Lybaert, Glenn Verstraete, Kim Deswarte, Stefan Lienenklaus, Nikunj M Shukla, Alex C D Salyer, Bart N Lambrecht and 4 more

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

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed, 2 pooled it
11.2field-weighted citation impact, top 1% 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

84 citing papers in PubMed, 2 syntheses or guidelines pooled it, 206 citations in OpenAlex.

  1. Controlling timing and location in vaccines.Advanced drug delivery reviews · 2020
    Pooled it
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  8. Structural immunotherapy: Harnessing chemical design to build powerful next-generation therapeutics.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
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  16. EngineeringVaccines · 2024
    Review
  17. Synthetic organic materials for targeting immunotherapies to lymph nodes.Chemistry of materials : a publication of the American Chemical Society · 2024
    Article
  18. Article
  19. Article
  20. Article

24 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

14 authors at 5 institutions in 3 countries.

Lutz NuhnDepartment of Pharmaceutics, Ghent University, 9000 Ghent, Belgium; Cancer Research Institute Ghent, 9052 Ghent, Belgium; lutz.nuhn@ugent.be sdavid@umn.edu stefaan.dekoker@ugent.be br.degeest@ugent.be.
Nane VanparijsDepartment of Pharmaceutics, Ghent University, 9000 Ghent, Belgium; Cancer Research Institute Ghent, 9052 Ghent, Belgium;
Ans De BeuckelaerDepartment of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium;
Lien LybaertDepartment of Pharmaceutics, Ghent University, 9000 Ghent, Belgium; Cancer Research Institute Ghent, 9052 Ghent, Belgium;
Glenn VerstraeteDepartment of Pharmaceutics, Ghent University, 9000 Ghent, Belgium; Cancer Research Institute Ghent, 9052 Ghent, Belgium;
Kim DeswarteVIB Inflammation Research Center, Ghent University, 9052 Zwijnaarde, Belgium; Department of Respiratory Medicine, University Hospital Ghent, 9000 Ghent, Belgium;
Stefan LienenklausInstitute for Laboratory Animal Science, Hannover Medical School, 30625 Hanover, Germany; Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, 30625 Hanover, Germany;
Nikunj M ShuklaDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455.
Alex C D SalyerDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455.
Bart N LambrechtVIB Inflammation Research Center, Ghent University, 9052 Zwijnaarde, Belgium; Department of Respiratory Medicine, University Hospital Ghent, 9000 Ghent, Belgium;
Johan GrootenDepartment of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium;
Sunil A DavidDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455 lutz.nuhn@ugent.be sdavid@umn.edu stefaan.dekoker@ugent.be br.degeest@ugent.be.
Stefaan De KokerDepartment of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium; lutz.nuhn@ugent.be sdavid@umn.edu stefaan.dekoker@ugent.be br.degeest@ugent.be.
Bruno G De GeestDepartment of Pharmaceutics, Ghent University, 9000 Ghent, Belgium; Cancer Research Institute Ghent, 9052 Ghent, Belgium; lutz.nuhn@ugent.be sdavid@umn.edu stefaan.dekoker@ugent.be br.degeest@ugent.be.
Ghent University · BEUniversity of Minnesota · USCancer Research Institute Ghent · BEGhent University Hospital · BEMedizinische Hochschule Hannover · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Agonists of Toll-like receptors (TLRs) are potent activators of the innate immune system and hold promise as vaccine adjuvant and for anticancer immunotherapy. Unfortunately, in soluble form they readily enter systemic circulation and cause systemic inflammatory toxicity. Here we demonstrate that by covalent ligation of a small-molecule imidazoquinoline-based TLR7/8 agonist to 50-nm-sized degradable polymeric nanogels the potency of the agonist to activate TLR7/8 in in vitro cultured dendritic cells is largely retained. Importantly, imidazoquinoline-ligated nanogels focused the in vivo immune activation on the draining lymph nodes while dramatically reducing systemic inflammation. Mechanistic studies revealed a prevalent passive diffusion of the nanogels to the draining lymph node. Moreover, immunization studies in mice have shown that relative to soluble TLR7/8 agonist, imidazoquinoline-ligated nanogels induce superior antibody and T-cell responses against a tuberculosis antigen. This approach opens possibilities to enhance the therapeutic benefit of small-molecule TLR agonist for a variety of applications.

Indexed as

Adjuvants, ImmunologicAnimalsAntigens, BacterialDendritic CellsGelsHydrogen-Ion ConcentrationImidazolesImmunizationLymph NodesMembrane GlycoproteinsMiceMice, Inbred C57BLNanostructuresT-LymphocytesToll-Like Receptor 7Toll-Like Receptor 8Adjuvants, ImmunologicAntigens, BacterialGelsImidazolesMembrane GlycoproteinsPPE44 protein, Mycobacterium tuberculosisTlr7 protein, mouseTLR8 protein, mouseToll-Like Receptor 7Toll-Like Receptor 8dendritic cellslymph nodenanotechnologyToll-like receptorvaccine

Identifiers

PMID27382168
PMCPMC4961133
OpenAlexW2472361557

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.