ArticleMolecular therapy. Nucleic acids2018
Immunogenicity Testing of Lipidoids In Vitro and In Silico: Modulating Lipidoid-Mediated TLR4 Activation by Nanoparticle Design.
Article in Molecular therapy. Nucleic acids, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 39 citations in OpenAlex.
- Elucidate the structural role of helper lipids in modulating hepatic expression following repeated intravenous administration of mRNA-LNPs.Materials today. Bio · 2026Article
- Engineering smart polymeric lipid nanoparticles for breast cancer: AI-guided formulation design, biological barriers, and translational constraints.Journal of nanobiotechnology · 2026Review
- Evaluation of in vitro liver models and non-human primates for predicting ADAR RNA editing efficiency in human liver.Scientific reports · 2025Article
- Endosomal Mechanisms in Heart Failure Pathophysiology.Current heart failure reports · 2025Review
- Ionizable lipid nanoparticles of mRNA vaccines elicit NF-κB and IRF responses through toll-like receptor 4.NPJ vaccines · 2025Article
- Advances in mRNA LNP-Based Cancer Vaccines: Mechanisms, Formulation Aspects, Challenges, and Future Directions.Journal of personalized medicine · 2024Review
- Amine headgroups in ionizable lipids drive immune responses to lipid nanoparticles by binding to the receptors TLR4 and CD1d.Nature biomedical engineering · 2024Article
- Application of Nanotechnology and Phytochemicals in Anticancer Therapy.Pharmaceutics · 2024Review
- Plasmid DNA ionisable lipid nanoparticles as non-inert carriers and potent immune activators for cancer immunotherapy.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Study of the Synergistic Immunomodulatory and Antifibrotic Effects of Dual-Loaded Budesonide and Serpine1 siRNA Lipid-Polymer Nanoparticles Targeting Macrophage Dysregulation in Tendinopathy.ACS applied materials & interfaces · 2024Article
- Lymph node macrophages drive innate immune responses to enhance the anti-tumor efficacy of mRNA vaccines.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Therapeutic effect of E-Lip-siRNA-sFlt1 on pre-eclampsia: targeted gene silencing and improved pregnancy outcomes.Nanomedicine (London, England) · 2024Article
- Design and lyophilization of lipid nanoparticles for mRNA vaccine and its robust immune response in mice and nonhuman primates.Molecular therapy. Nucleic acids · 2022Article
- The replacement of helper lipids with charged alternatives in lipid nanoparticles facilitates targeted mRNA delivery to the spleen and lungs.Journal of controlled release : official journal of the Controlled Release Society · 2022Article
- Epithelial-Specific TLR4 Knockout Challenges Current Evidence of TLR4 Homeostatic Control of Gut Permeability.Inflammatory intestinal diseases · 2021Article
- Functionalized lipid nanoparticles for subcutaneous administration of mRNA to achieve systemic exposures of a therapeutic protein.Molecular therapy. Nucleic acids · 2021Article
- Tuning the Immunostimulation Properties of Cationic Lipid Nanocarriers for Nucleic Acid Delivery.Frontiers in immunology · 2021Article
- Nanoparticles as Adjuvants and Nanodelivery Systems for mRNA-Based Vaccines.Pharmaceutics · 2020Review
- Nanotechnology as a Platform for the Development of Injectable Parenteral Formulations: A Comprehensive Review of the Know-Hows and State of the Art.Pharmaceutics · 2020Review
- Opportunities and Challenges in the Delivery of mRNA-based Vaccines.Pharmaceutics · 2020Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Therapeutics based on small interfering RNA (siRNA) have promising potential as antiviral and anti-inflammatory agents. To deliver siRNA across cell membranes to reach the RNAi pathway in the cytosol of target cells, non-viral nanoparticulate delivery approaches are explored. Recently, we showed that encapsulation of siRNA in lipid-polymer hybrid nanoparticles (LPNs), based on poly(DL-lactic-co-glycolic acid) (PLGA) and cationic lipid-like materials (lipidoids), remarkably enhances intracellular delivery of siRNA as compared to siRNA delivery with LPNs modified with dioleoyltrimethylammoniumpropane (DOTAP) as the lipid component. However, the potential immune modulation by these cationic lipids remains unexplored. By testing lipidoids and DOTAP for innate immune-receptor-activating properties in vitro, we found that neither lipidoids nor DOTAP activate human Toll-like receptor (TLR) 2, 3, 7, and 9. However, in contrast to DOTAP, lipidoids are strong agonists for TLR4 and activate murine antigen-presenting cells in vitro. This agonistic effect was further confirmed in silico using a prediction model based on crystal structures. Also, lipidoids formulated as lipoplexes or as stable nucleic acid lipid particles, which was the reference formulation for siRNA delivery, proved to activate TLR4. However, by combining lipidoids with PLGA into LPNs, TLR4 activation was abrogated. Thus, lipidoid-mediated TLR4 activation during siRNA delivery may be modulated via optimization of the formulation design.
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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.