ArticleNature biotechnology2013
Image-based analysis of lipid nanoparticle-mediated siRNA delivery, intracellular trafficking and endosomal escape.
Article in Nature biotechnology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 752 papers, 2 of them syntheses that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
752 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,518 citations in OpenAlex.
- Mapping programmable mRNA research relevant to cancer-associated immune escape: a dual-database bibliometric and topic modeling analysis.Frontiers in oncology · 2026Pooled it
- Dissolving microneedles for nucleic acid delivery: A systematic search, review, and data synthesis.Acta biomaterialia · 2025Pooled it
- Cationized gelatin nanosphere-mediated release-controlled RNA interference targeting mTORC1 protects against intervertebral disc degeneration.Bioactive materials · 2027Article
- siRNA did not fail in cancer. It was given the wrong job.Molecular therapy. Nucleic acids · 2026Article
- Novel lipid nanoparticle in a mRNA cancer vaccine drives tumor control via type I IFNs and effector CD8Molecular therapy. Nucleic acids · 2026Article
- siRNA therapeutics for metabolic dysfunction-associated Steatohepatitis: Targets, delivery, clinical evidence, and translational challenges.Biochemistry and biophysics reports · 2026Review
- Cyano-modulated Zn(II)-Schiff base complexes for lysosome-targeted fluorescence imaging and pH-responsive camptothecin delivery.International journal of pharmaceutics: X · 2026Article
- Beyond Nanosizing: Mechanism-Guided Design and Rational Selection of Polymeric and Lipid Nanocarriers for Translatable Drug Delivery.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Review
- Cancer nanomedicine and RNA/Lipid nanoparticle platforms in oncology: developmental evolution, translational barriers, and precision-therapy opportunities.Journal of the Egyptian National Cancer Institute · 2026Review
- Why does siRNA delivery still fail in neurodegenerative diseases? Biological barriers, nanocarrier engineering, and future translational directions.Molecular biology reports · 2026Review
- New approach methodologies in nanomedicine: bridging the gap betweenChemical Society reviews · 2026Review
- Bioactive lipid-derived nanoparticles for RNA delivery.Materials today (Kidlington, England) · 2026Article
- Structural evolution of ionizable lipids for nucleic acid delivery.Nature reviews. Chemistry · 2026Review
- Engineering mRNA-LNP Medicines for the Ageing Brain: Opportunities and Challenges for Neurodegenerative Diseases.Exploration (Beijing, China) · 2026Review
- Harnessing the endosomal escape compartment as a strategy to enhance RNA delivery via lipid nanoparticles.Molecular therapy. Nucleic acids · 2026Article
- Extracellular Vesicle-Lipid Hybrid Systems for RNA Delivery in Cancer: Structural Classification, Functional Delivery, and Translational Challenges.Pharmaceutics · 2026Review
- Active pH Modulation by Proton Channel-Peptide Nucleic Acid Complex for Effective siRNA Endosomal Escape.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Beyond the genetic code: orchestrating epigenetic and immune landscapes with multivalent mRNA-exosome vaccines.Precision clinical medicine · 2026Review
- Polymeric mesoscale nanoparticles exhibit dynamin- and macropinocytosis-dependent endocytosis.Nanomedicine : nanotechnology, biology, and medicine · 2026Article
- Lipid nanoparticles as active biointerfaces: From membrane interaction to systemic dysregulation.Acta pharmaceutica Sinica. B · 2026Review
692 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Delivery of short interfering RNAs (siRNAs) remains a key challenge in the development of RNA interference (RNAi) therapeutics. A better understanding of the mechanisms of siRNA cellular uptake, intracellular transport and endosomal release could critically contribute to the improvement of delivery methods. Here we monitored the uptake of lipid nanoparticles (LNPs) loaded with traceable siRNAs in different cell types in vitro and in mouse liver by quantitative fluorescence imaging and electron microscopy. We found that LNPs enter cells by both constitutive and inducible pathways in a cell type-specific manner using clathrin-mediated endocytosis as well as macropinocytosis. By directly detecting colloidal-gold particles conjugated to siRNAs, we estimated that escape of siRNAs from endosomes into the cytosol occurs at low efficiency (1-2%) and only during a limited window of time when the LNPs reside in a specific compartment sharing early and late endosomal characteristics. Our results provide insights into LNP-mediated siRNA delivery that can guide development of the next generation of delivery systems for RNAi 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.