ArticleJournal of the American Chemical Society2025
Lipid-siRNA Organization Modulates the Intracellular Dynamics of Lipid Nanoparticles.
Article in Journal of the American Chemical Society, 2025. 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 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.
- Dual pKa Lipid Nanoparticles for Lung-tropic mRNA Delivery and pH-Programmed Endosomal Escape.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- From Morphology to Mechanism: Cryo-Electron Microscopy Insights into Lipid Nanoparticles for RNA Delivery.ACS nano · 2026Review
- E-selectin and transferrin receptor functionalized synthetic miRNA nanoshuttles with therapeutic potential in stroke.Drug delivery and translational research · 2026Article
- Mechanistic Insight Into Ionizable Cationic Lipid-Mediated Endosomal Escape via Transient Lipid Complexes.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Biomimetic PD-1 macrophage nanoplatform for Cip2a silencing and immune activation in oral squamous cell carcinoma.Journal of nanobiotechnology · 2026Article
- Selective mRNA Delivery to Activated Macrophages via Hyaluronic Acid-Functionalized Lipid Nanoparticles with Optimized PEGylation.Biomacromolecules · 2026Article
- Structural Change of ApoE-Lipid Nanoparticles Alters Receptor-Mediated Endocytosis and Induces Endosomal Disruption.Journal of the American Chemical Society · 2026Article
- The Nanoparticle Delivery Gap in Immune Cell Engineering: From Uptake to Endosomal Escape.International journal of nanomedicine · 2026Review
- Size control of lipid nanoparticles via simulation-based design of a microfluidic chip and its effect on mRNA delivery in vitro and in vivo.Journal of nanobiotechnology · 2025Article
- Research Progress on Nasal Delivery of siRNA Nanocarrier Systems for the Treatment of Neurodegenerative Diseases.Pharmaceutics · 2025Review
- Translational Advances in Lipid Nanoparticle Drug Delivery Systems for Cancer Therapy: Current Status and Future Horizons.Pharmaceutics · 2025Review
- Formulation methods for peptide-modified lipid nanoparticles.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Endo/Lysosomal-Escapable Lipid Nanoparticle Platforms for Enhancing mRNA Delivery in Cancer Therapy.Pharmaceutics · 2025Review
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipid nanoparticles (LNPs) are widely used for delivering therapeutic nucleic acids, yet the relationship between their internal structure and intracellular behavior, particularly before RNA release, remains unclear. Here, we elucidate how lipid-siRNA organization within LNPs can modulate their intracellular delivery dynamics. We use cryo-electron microscopy and photochemical assays to reveal that increased siRNA loading can reduce helper lipids' distribution to the LNP surface, while siRNA consistently localizes near the surface. These alterations in lipid-siRNA organization affect LNP membrane fluidity, enhancing LNP fusion with cellular membranes and promoting cytosolic siRNA delivery, primarily via macropinocytosis. Using photosensitive lipids and live cell imaging, we demonstrate that lipid-siRNA organization regulates LNP responsiveness to external stimuli, significantly affecting siRNA endosomal escape efficiency upon light activation. We further confirm this observation using convex lens-induced confinement microscopy and single-particle imaging. Overall, our findings provide critical insights into how lipid-siRNA organization shapes LNP intracellular dynamics, offering rational design principles for optimizing LNP-based RNA therapeutics.
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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.