ArticleBiomaterials2021
Kupffer cell release of platelet activating factor drives dose limiting toxicities of nucleic acid nanocarriers.
Article in Biomaterials, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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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.
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.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
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- Nanocarrier-mediated targeting of NF-κB and JAK/STAT signaling pathways in hepatocellular carcinoma: mechanisms and therapeutic strategies.Journal of experimental & clinical cancer research : CR · 2026Review
- Fabrication of RIG-I-Activating Nanoparticles for Intratumoral Immunotherapy via Flash Nanoprecipitation.Molecular pharmaceutics · 2025Article
- Covalent Polymer-RNA Conjugates for Potent Activation of the RIG-I Pathway.Advanced healthcare materials · 2025Article
- Structural optimization of siRNA conjugates for albumin binding achieves effective MCL1-directed cancer therapy.Nature communications · 2024Article
- Core polymer optimization of ternary siRNA nanoparticles enhances in vivo safety, pharmacokinetics, and tumor gene silencing.Biomaterials · 2023Article
- Lipid oxidation dysregulation: an emerging player in the pathophysiology of sepsis.Frontiers in immunology · 2023Review
- Article
- Stimulating TAM-mediated anti-tumor immunity with mannose-decorated nanoparticles in ovarian cancer.BMC cancer · 2022Article
- Understanding Nanomaterial-Liver Interactions to Facilitate the Development of Safer Nanoapplications.Advanced materials (Deerfield Beach, Fla.) · 2022Review
- Therapeutic RNA Delivery for COVID and Other Diseases.Advanced healthcare materials · 2021Review
- Optimizing an Antioxidant TEMPO Copolymer for Reactive Oxygen Species Scavenging and Anti-Inflammatory EffectsBioconjugate chemistry · 2021Article
- Replacement of L-amino acid peptides with D-amino acid peptides mitigates anti-PEG antibody generation against polymer-peptide conjugates in mice.Journal of controlled release : official journal of the Controlled Release Society · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
This work establishes that Kupffer cell release of platelet activating factor (PAF), a lipidic molecule with pro-inflammatory and vasoactive signaling properties, dictates dose-limiting siRNA nanocarrier-associated toxicities. High-dose intravenous injection of siRNA-polymer nano-polyplexes (si-NPs) elicited acute, shock-like symptoms in mice, associated with increased plasma PAF and consequently reduced PAF acetylhydrolase (PAF-AH) activity. These symptoms were completely prevented by prophylactic PAF receptor inhibition or Kupffer cell depletion. Assessment of varied si-NP chemistries confirmed that toxicity level correlated to relative uptake of the carrier by liver Kupffer cells and that this toxicity mechanism is dependent on carrier endosome disruptive function. 4T1 tumor-bearing mice, which exhibit increased circulating leukocytes, displayed greater sensitivity to these toxicities. PAF-mediated toxicities were generalizable to commercial delivery reagent in vivo-jetPEI® and an MC3 lipid formulation matched to an FDA-approved nanomedicine. These collective results establish Kupffer cell release of PAF as a key mediator of siRNA nanocarrier toxicity and identify PAFR inhibition as an effective strategy to increase siRNA nanocarrier tolerated dose.
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What OpenQuestion holds
Registered trials
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.