ArticleJournal of controlled release : official journal of the Controlled Release Society2017
Toll-like receptor 2 promiscuity is responsible for the immunostimulatory activity of nucleic acid nanocarriers.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 25 citations in OpenAlex.
- Dendritic Lipopeptide Nanovaccines Orchestrate Multi-Pattern Recognition Receptors Activation and Potentiate Antitumor Immunity.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- From bench to bedside: Unveiling the background and benefits of nanovaccines tested in clinics.Asian journal of pharmaceutical sciences · 2026Review
- Lipid Nanoparticles Formulated with a Novel Cholesterol-Tailed Ionizable Lipid Markedly Increase mRNA Delivery Both in vitro and in vivo.International journal of nanomedicine · 2025Article
- Engineering a spleen-selective mRNA-LNPs vaccine by decoupling the inflammation from cellular immunity-mediated cancer immunotherapy.Theranostics · 2025Article
- Effect of Lipid Nanoparticle Physico-Chemical Properties and Composition on Their Interaction with the Immune System.Pharmaceutics · 2024Review
- Amine headgroups in ionizable lipids drive immune responses to lipid nanoparticles by binding to the receptors TLR4 and CD1d.Nature biomedical engineering · 2024Article
- Emerging Cationic Nanovaccines.Pharmaceutics · 2024Review
- Review: Current trends, challenges, and success stories in adjuvant research.Frontiers in immunology · 2023Review
- Transcriptomic analysis of the innate immune signatures of a SARS-CoV-2 protein subunit vaccine ZF2001 and an mRNA vaccine RRV.Emerging microbes & infections · 2022Article
- The role of lipid components in lipid nanoparticles for vaccines and gene therapy.Advanced drug delivery reviews · 2022Review
- Lipid-protein interactions regulating the canonical and the non-canonical NLRP3 inflammasome.Progress in lipid research · 2022Review
- Cationic Nanoparticle-Based Cancer Vaccines.Pharmaceutics · 2021Review
- Saturation of acyl chains converts cardiolipin from an antagonist to an activator of Toll-like receptor-4.Cellular and molecular life sciences : CMLS · 2019Article
- Antigen Priming with Enantiospecific Cationic Lipid Nanoparticles Induces Potent Antitumor CTL Responses through Novel Induction of a Type I IFN Response.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Lipopolyamines (LPAs) are cationic lipids; they interact spontaneously with nucleic acids to form lipoplexes used for gene delivery. The main hurdle to using lipoplexes in gene therapy lies in their immunostimulatory properties, so far attributed to the nucleic acid cargo, while cationic lipids were considered as inert to the immune system. Here we demonstrate for the first time that di-C18 LPAs trigger pro-inflammatory responses through Toll-like receptor 2 (TLR2) activation, and this whether they are bound to nucleic acids or not. Molecular docking experiments suggest potential TLR2 binding modes reminiscent of bacterial lipopeptide sensing. The di-C18 LPAs share the ability of burying their lipid chains in the hydrophobic cavity of TLR2 and, in some cases, TLR1, at the vicinity of the dimerization interface; the cationic headgroups form multiple hydrogen bonds, thus crosslinking TLRs into functional complexes. Unravelling the molecular basis of TLR1 and TLR6-driven heterodimerization upon LPA binding underlines the highly collaborative and promiscuous ligand binding mechanism. The prevalence of non-specific main chain-mediated interactions demonstrates that potentially any saturated LPA currently used or proposed as transfection agent is likely to activate TLR2 during transfection. Hence our study emphasizes the urgent need to test the inflammatory properties of transfection agents and proposes the use of docking analysis as a preliminary screening tool for the synthesis of new non-immunostimulatory nanocarriers.
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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.