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

Animals Endotoxemia / immunology Enzyme-Linked Immunosorbent Assay Female Flow Cytometry Immunity, Innate / genetics Inflammation / immunology Mice Mice, Inbred C57BL Nanoparticles / chemistry Polyesters / chemistry Polylactic Acid-Polyglycolic Acid Copolymer / chemistry RAW 264.7 Cells Sepsis / immunology Toll-Like Receptors / metabolism
Cellular reprogramming Endotoxemia Immunomodulation Inflammation Nanoparticles Sepsis

Journal

Biomaterials
ISSN: 1878-5905
Titre abrégé: Biomaterials
Pays: Netherlands
ID NLM: 8100316

Informations de publication

Date de publication:
10 2019
Historique:
received: 07 03 2019
revised: 28 06 2019
accepted: 01 07 2019
pubmed: 14 7 2019
medline: 22 9 2020
entrez: 14 7 2019
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.biomaterials.2019.119333 PMID: 31301576 PMC: PMC6679939
pubmed: 31301576
pii: S0142-9612(19)30432-6
doi: 10.1016/j.biomaterials.2019.119333
pmc: PMC6679939
mid: NIHMS1534672
pii:
doi:

Substances chimiques

Polyesters 0
Toll-Like Receptors 0
Polylactic Acid-Polyglycolic Acid Copolymer 1SIA8062RS
poly(lactide) 459TN2L5F5

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

119333

Subventions

Organisme : NIBIB NIH HHS
ID : R01 EB013198
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK071212
Pays : United States

Informations de copyright

Copyright © 2019 Elsevier Ltd. All rights reserved.

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Auteurs

Liam M Casey (LM)

Department of Chemical Engineering, University of Michigan, 2300 Hayward Avenue, Ann Arbor, MI, 48105, USA.

Sandeep Kakade (S)

Department of Biomedical Engineering, University of Michigan, 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, MI, 48109-2099, USA.

Joseph T Decker (JT)

Department of Biomedical Engineering, University of Michigan, 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, MI, 48109-2099, USA.

Justin A Rose (JA)

Department of Biomedical Engineering, University of Michigan, 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, MI, 48109-2099, USA.

Kyle Deans (K)

Department of Biomedical Engineering, University of Michigan, 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, MI, 48109-2099, USA.

Lonnie D Shea (LD)

Department 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 Pearson (RM)

Department 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.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Cargo-less nanoparticles program innate immune...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Sepsie › Bactériémie › Endotoxémie › Cargo-less nanoparticles program innate immune...
questionsmedicales.fr › Techniques d'investigation › Techniques de sonde moléculaire › Dosage immunologique › Techniques d'immunoadsorption › Test ELISA › Cargo-less nanoparticles program innate immune...
questionsmedicales.fr › Techniques d'investigation › Techniques cytologiques › Cytophotométrie › Cytométrie en flux › Cargo-less nanoparticles program innate immune...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Immunité innée › Cargo-less nanoparticles program innate immune...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Cargo-less nanoparticles program innate immune...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Cargo-less nanoparticles program innate immune...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Cargo-less nanoparticles program innate immune...
questionsmedicales.fr › Technologie, industrie et agriculture › Produits manufacturés › Nanostructures › Nanoparticules › Cargo-less nanoparticles program innate immune...
questionsmedicales.fr › Technologie, industrie et agriculture › Produits manufacturés › Matériaux biomédicaux et dentaires › Polymères › Polyesters › Cargo-less nanoparticles program innate immune...
questionsmedicales.fr › Technologie, industrie et agriculture › Produits manufacturés › Matériaux biomédicaux et dentaires › Polymères › Polyesters › Acide polyglycolique › Copolymère d'acide poly(lactique-co-glycolique) › Cargo-less nanoparticles program innate immune...
questionsmedicales.fr › Cellules › Cellules RAW 264.7 › Cargo-less nanoparticles program innate immune...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Sepsie › Cargo-less nanoparticles program innate immune...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs de reconnaissance de motifs moléculaires › Récepteurs de type Toll › Cargo-less nanoparticles program innate immune...