ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
Relationship Between the Physicochemical Properties of Lipid Nanoparticles and the Quality of siRNA Delivery to Liver Cells.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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
27 citing papers in PubMed.
- Membrane Fusion-Inspired Nanomaterials: Emerging Strategies for Infectious Disease and Cancer Diagnostics.Advanced healthcare materials · 2026Review
- GPAM upregulation enhances hepatic fat deposition and reduces visceral adipose tissue in response to trans-fatty acids.Journal of gastroenterology · 2025Article
- mRNA vaccines: immunogenicity and quality characteristics.Journal of nanobiotechnology · 2025Review
- The impact of chemical reactivity on the quality and stability of RNA-LNP pharmaceuticals.Nature reviews. Chemistry · 2025Review
- High-Throughput Strategies for Streamlining Lipid Nanoparticle Development Pipeline.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Emerging Strategies of Cell and Gene Therapy Targeting Tumor Immune Microenvironment.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Therapeutic induction of antigen-specific immune tolerance.Nature reviews. Immunology · 2024Review
- Strategies to reduce the risks of mRNA drug and vaccine toxicity.Nature reviews. Drug discovery · 2024Review
- Fine tuning of the net charge alternation of polyzwitterion surfaced lipid nanoparticles to enhance cellular uptake and membrane fusion potential.Science and technology of advanced materials · 2024Article
- 'Passive' nanoparticles for organ-selective systemic delivery: design, mechanism and perspective.Chemical Society reviews · 2023Review
- mRNA nanodelivery systems: targeting strategies and administration routes.Biomaterials research · 2023Review
- Lipid-based nucleic acid therapeutics with in vivo efficacy.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2023Review
- Passive, active and endogenous organ-targeted lipid and polymer nanoparticles for delivery of genetic drugs.Nature reviews. Materials · 2023Review
- Structure and Function of Cationic and Ionizable Lipids for Nucleic Acid Delivery.Pharmaceutical research · 2023Review
- siRNA Functionalized Lipid Nanoparticles (LNPs) in Management of Diseases.Pharmaceutics · 2022Review
- mRNA-Loaded Lipid Nanoparticles Targeting Dendritic Cells for Cancer Immunotherapy.Pharmaceutics · 2022Article
- Functional siRNA Delivery by Extracellular Vesicle-Liposome Hybrid Nanoparticles.Advanced healthcare materials · 2022Article
- Nanoparticles for Inducing Antigen-Specific T Cell Tolerance in Autoimmune Diseases.Frontiers in immunology · 2022Review
- Endothelial dysfunction in pathological processes of chronic liver disease during aging.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Review
- Lipids and Lipid Derivatives for RNA Delivery.Chemical reviews · 2021Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While a variety of short interfering RNA (siRNA) delivery compounds have been developed, a deep understanding of the key parameters that determine the quality of siRNA delivery are not known with certainty. Therefore, an understanding of the factors required for the efficient, selective, and safe delivery of siRNA is a great challenge for successful siRNA delivery. Herein, we report on the development of two pH-sensitive cationic lipids and their use in examining the impact of the acid dissociation constant (pKa) value, lipase sensitivity and the size of lipid nanoparticles on the biodistribution, and efficiency and cell specificity of gene silencing in the liver. An increase in the pKa value resulted in a significant change in the intrahepatic localization of siRNA and gene-silencing efficiency in hepatocytes and liver sinusoidal endothelial cells (LSECs). The sensitivity of the pH-sensitive cationic lipid to lipases was a major factor in achieving hepatocyte-specific gene silencing. Increasing the particle size can improve the LSEC specificity of gene silencing. As a consequence, we succeeded in developing both a highly efficient, hepatocyte-specific formulation, and the most efficacious LSEC-targeted formulation reported to date. These findings will facilitate the development of more sophisticated siRNA delivery systems.
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Registered trials
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