ArticleACS bio & med chem Au2025
Exploring the Effects of Incorporating Different Bioactive Phospholipids into Messenger Ribonucleic Acid Lipid Nanoparticle (mRNA LNP) Formulations.
Article in ACS bio & med chem Au, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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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
4 citing papers in PubMed.
- Bioactive lipid-derived nanoparticles for RNA delivery.Materials today (Kidlington, England) · 2026Article
- Delivering the future of immunotherapy: A state-of-the-art review of gene editing in immune cells with lipid nanoparticles.Materials today. Bio · 2026Review
- Mechanistic Insight Into Ionizable Cationic Lipid-Mediated Endosomal Escape via Transient Lipid Complexes.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Smart CAR-T Nanosymbionts: archetypes and proto-models.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The current rapid advancement in ribonucleic acid (RNA) therapeutics research depends on innovations in drug delivery, especially the development of a lipid-nanoparticle (LNP)-based system. The conventional LNP formulation typically contains four components, including an ionizable cationic lipid, a phospholipid, cholesterol or a cholesterol derivative, and poly(ethylene glycol) (PEG)-lipid, with each contributing to the formulation's overall stability and effectiveness. Among these four types of lipids, the phospholipid component is often known to provide structural support for the nanoparticles but is also a class of bioactive molecules with strong cell signaling potential. This study explores the possibility of incorporating some known structurally related bioactive phospholipids as the fifth component of a conventional four-component LNP formulation and assesses the impacts of such an approach on the physicochemical properties and biological functions of the mRNA LNP formulation. We screened a library of mRNA LNP formulations containing 7 different structurally related bioactive phospholipids at molar concentrations of 5%, 15% and 30% in addition to a conventional four-component LNP formulation (base). We observed differences in physicochemical properties between the mRNA LNP formulations that could be attributed to both the types of phospholipids examined and the molar concentrations used. Cryo-EM analysis revealed structural similarity between the Base formulation and the other formulations. We also characterized the protein expression level in HeLa cells and picked up a distinct cytokine panel signature for each formulation in human peripheral blood mononuclear cells (hPBMCs). Further immunophenotyping analysis showed that most cells that were transfected were CD4+ T cells, and the addition of the different bioactive phospholipids slightly altered cellular tropism. This exploratory study illustrates how adding the bioactive phospholipid can be used to modulate the LNP function, further expanding the design space for RNA LNP formulations and potentiating LNPs for use as RNA therapeutics.
Identifiers
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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.