ArticleNature biotechnology2013
Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling.
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 412 papers, 1 of them a synthesis 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.
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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
412 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Development of siRNA therapeutics to combat microbial infections: a bibliometric analysis.Frontiers in cellular and infection microbiology · 2025Pooled it
- DNA oligonucleotides encoding suppressor tRNA induce readthrough of premature termination codon.Molecular therapy. Nucleic acids · 2026Article
- Development of mRNA vaccines against herpes zoster.Human vaccines & immunotherapeutics · 2026Review
- Bioactive lipid-derived nanoparticles for RNA delivery.Materials today (Kidlington, England) · 2026Article
- Harnessing the endosomal escape compartment as a strategy to enhance RNA delivery via lipid nanoparticles.Molecular therapy. Nucleic acids · 2026Article
- Breaking Biological Barriers: Engineering Nanocarriers for Efficient Drug and Gene Delivery through Nano-Bio Interfaces and Biophysical Design.Applied physics reviews · 2026Article
- Lipid nanoparticles as active biointerfaces: From membrane interaction to systemic dysregulation.Acta pharmaceutica Sinica. B · 2026Review
- Navigating Lipid Nanostructure Design Space Through Continuous Microfluidic Automation.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Defect-Engineered BiOAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- pH-Sensitive Amino Lipid-Driven Pore Formation Enables Endosomal Escape of Lipid Nanoparticles.Nature communications · 2026Article
- Biomacromolecule-MOF Composites for Intracellular Delivery: From Empirical Construction to Rational Design and AI-Assisted Screening.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Quadruplex Bioactive FAND for Treating Acute Liver Failure Induced by Acetaminophen or Hepatectomy.Exploration (Beijing, China) · 2026Article
- De Novo Lipid Switch Design for Reactive Oxygen Species-Triggered Liposomal Release.Bioconjugate chemistry · 2026Article
- Hypoxia-injured pulmonary vascular targeting and microenvironment-responsive nanoparticle to treat hypoxic pulmonary hypertension.Journal of nanobiotechnology · 2026Article
- Epigenetic editing approaches maturity: AI-driven precision design, delivery innovation, and the road to clinical translation.Clinical epigenetics · 2026Review
- Storage Buffer Composition Impacts Internal Structure, Freeze-Thaw Stability, and Transfection Efficiency of mRNA-Lipid Nanoparticles.ACS nano · 2026Article
- Engineered Lipid Nanoparticles with Promoted Endosomal Escape and R283S-Mediated Stimulator of Interferon Genes (STING) Activation for Pancreatic Cancer Immunotherapy.Pharmaceutics · 2026Article
- Injectable pre-vascularized alginate-collagen hydrogel with sustained delivery of miR-133a-loaded lipid nanoparticles for myocardial repair.Drug delivery and translational research · 2026Article
- From LNPs to hybrid nanocarriers: development, challenges and redesign of non-viral gene delivery.Journal of nanobiotechnology · 2026Review
- Enhanced endosomal escape for nanoparticle-enabled co-delivery of doxorubicin and siRNA to overcome multidrug resistance.Materials today. Advances · 2026Article
352 more citing papers are in PubMed but not listed here.
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14 authors.
Funding
Abstract
Despite efforts to understand the interactions between nanoparticles and cells, the cellular processes that determine the efficiency of intracellular drug delivery remain unclear. Here we examine cellular uptake of short interfering RNA (siRNA) delivered in lipid nanoparticles (LNPs) using cellular trafficking probes in combination with automated high-throughput confocal microscopy. We also employed defined perturbations of cellular pathways paired with systems biology approaches to uncover protein-protein and protein-small molecule interactions. We show that multiple cell signaling effectors are required for initial cellular entry of LNPs through macropinocytosis, including proton pumps, mTOR and cathepsins. siRNA delivery is substantially reduced as ≅70% of the internalized siRNA undergoes exocytosis through egress of LNPs from late endosomes/lysosomes. Niemann-Pick type C1 (NPC1) is shown to be an important regulator of the major recycling pathways of LNP-delivered siRNAs. NPC1-deficient cells show enhanced cellular retention of LNPs inside late endosomes and lysosomes, and increased gene silencing of the target gene. Our data suggest that siRNA delivery efficiency might be improved by designing delivery vehicles that can escape the recycling pathways.
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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.