Evidence map›Paper›PMID 31301576›Full record

ArticleBiomaterials2019

Cargo-less nanoparticles program innate immune cell responses to toll-like receptor activation.

Liam M Casey, Sandeep Kakade, Joseph T Decker, Justin A Rose, Kyle Deans, Lonnie D Shea, Ryan M Pearson

Open access · greenAbstract read
In one paragraph

Article in Biomaterials, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

56 citing papers in PubMed, 80 citations in OpenAlex.

  1. Article
  2. Article
  3. Engineered cargo-free nanoparticle decoys for phagocytic modulation of macrophages.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Engineered immunological niche directs therapeutic development in models of progressive multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Trace elements and metal nanoparticles: mechanistic approaches to mitigating chemotherapy-induced toxicity-a review of literature evidence.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024
    Review
  20. Review
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

7 authors at 2 institutions in 1 country.

Liam M CaseyDepartment of Chemical Engineering, University of Michigan, 2300 Hayward Avenue, Ann Arbor, MI, 48105, USA.
Sandeep KakadeDepartment of Biomedical Engineering, University of Michigan, 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, MI, 48109-2099, USA.
Joseph T DeckerDepartment of Biomedical Engineering, University of Michigan, 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, MI, 48109-2099, USA.
Justin A RoseDepartment of Biomedical Engineering, University of Michigan, 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, MI, 48109-2099, USA.
Kyle DeansDepartment of Biomedical Engineering, University of Michigan, 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, MI, 48109-2099, USA.
Lonnie D SheaDepartment of Chemical Engineering, University of Michigan, 2300 Hayward Avenue, Ann Arbor, MI, 48105, USA; Department of Biomedical Engineering, University of Michigan, 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, MI, 48109-2099, USA. Electronic address: ldshea@umich.edu.
Ryan M PearsonDepartment of Biomedical Engineering, University of Michigan, 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, MI, 48109-2099, USA; Department of Pharmaceutical Sciences, University of Maryland, 20 N. Pine Street, Baltimore, MD, 21201, USA. Electronic address: rpearson@rx.umaryland.edu.
University of Michigan–Ann Arbor · USUniversity of Maryland, Baltimore · US

Funding

Postdoc Stipend Supplement: Developmental Origins of Metabolic Disorders T32T32DK071212 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DAVID P OLSON, Kanakadurga Singer · 2005 to 2026
$5.4M
Antigen Loaded Particles for Tolerance InductionR01EB013198 · NIBIB · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MILLER, STEPHEN D, SHEA, LONNIE D · 2011 to 2018
$4.1M
NIBIB NIH HHS R01 EB013198NIDDK NIH HHS T32 DK071212
6 · The paper itself

Abstract

Developing biomaterials to control the responsiveness of innate immune cells represents a clinically relevant approach to treat diseases with an underlying inflammatory basis, such as sepsis. Sepsis can involve activation of Toll-like receptor (TLR) signaling, which activates numerous inflammatory pathways. The breadth of this inflammation has limited the efficacy of pharmacological interventions that target a single molecular pathway. Here, we developed cargo-less particles as a single-agent, multi-target platform to elicit broad anti-inflammatory action against innate immune cells challenged by multiple TLR agonists. The particles, prepared from poly(lactic-co-glycolic acid) (PLGA) and poly(lactic acid) (PLA), displayed potent molecular weight-, polymer composition-, and charge-dependent immunomodulatory properties, including downregulation of TLR-induced costimulatory molecule expression and cytokine secretion. Particles prepared using the anionic surfactant poly(ethylene-alt-maleic acid) (PEMA) significantly blunted the responses of antigen presenting cells to TLR4 (lipopolysaccharide) and TLR9 (CpG-ODN) agonists, demonstrating broad inhibitory activity to both extracellular and intracellular TLR ligands. Interestingly, particles prepared using poly(vinyl alcohol) (PVA), a neutrally-charged surfactant, only marginally inhibited inflammatory cytokine secretions. The biochemical pathways modulated by particles were investigated using TRanscriptional Activity CEll aRrays (TRACER), which implicated IRF1, STAT1, and AP-1 in the mechanism of action for PLA-PEMA particles. Using an LPS-induced endotoxemia mouse model, administration of PLA-PEMA particles prior to or following a lethal challenge resulted in significantly improved mean survival. Cargo-less particles affect multiple biological pathways involved in the development of inflammatory responses by innate immune cells and represent a potentially promising therapeutic strategy to treat severe inflammation.

Indexed as

AnimalsEndotoxemiaEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryImmunity, InnateInflammationMiceMice, Inbred C57BLNanoparticlesPolyestersPolylactic Acid-Polyglycolic Acid CopolymerRAW 264.7 CellsSepsisToll-Like ReceptorsPolyestersPolylactic Acid-Polyglycolic Acid Copolymerpoly(lactide)Toll-Like ReceptorsCellular reprogrammingEndotoxemiaImmunomodulationInflammationNanoparticlesSepsis

Identifiers

PMID31301576
PMCPMC6679939
OpenAlexW2954545712

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.