ArticleBiomaterials2017
Bolstering cholesteryl ester hydrolysis in liver: A hepatocyte-targeting gene delivery strategy for potential alleviation of atherosclerosis.
Article in Biomaterials, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 32 citations in OpenAlex.
- Enhanced Cholesterol Efflux and Atherosclerosis Regression via CEH Gene Delivery Using Galactose-Functionalized Dendrimeric Nanoparticles.ACS pharmacology & translational science · 2025Article
- Galactosylated hydroxyl-polyamidoamine dendrimer targets hepatocytes and improves therapeutic outcomes in a severe model of acetaminophen poisoning-induced liver failure.Bioengineering & translational medicine · 2023Article
- Oxidized Low-Density Lipoproteins Trigger Hepatocellular Oxidative Stress with the Formation of Cholesteryl Ester Hydroperoxide-Enriched Lipid Droplets.International journal of molecular sciences · 2023Article
- Kidney-Targeted Delivery of Prolyl Hydroxylase Domain Protein 2 Small Interfering RNA with Nanoparticles Alleviated Renal Ischemia/Reperfusion Injury.The Journal of pharmacology and experimental therapeutics · 2021Article
- Recent advances in nanomaterials for therapy and diagnosis for atherosclerosis.Advanced drug delivery reviews · 2021Review
- Progress in drug delivery system for fibrosis therapy.Asian journal of pharmaceutical sciences · 2021Review
- Nanotechnology in Drug Delivery for Liver Fibrosis.Frontiers in molecular biosciences · 2021Review
- Nanoparticle-based "Two-pronged" approach to regress atherosclerosis by simultaneous modulation of cholesterol influx and efflux.Biomaterials · 2020Article
- Lipids and Lipid-Processing Pathways in Drug Delivery and Therapeutics.International journal of molecular sciences · 2020Review
- Development of mannose functionalized dendrimeric nanoparticles for targeted delivery to macrophages: use of this platform to modulate atherosclerosis.Translational research : the journal of laboratory and clinical medicine · 2018Article
- Platinum-Based Nanovectors Engineered with Immuno-Modulating Adjuvant for Inhibiting Tumor growth and Promoting Immunity.Theranostics · 2018Article
- Lipidomics in translational research and the clinical significance of lipid-based biomarkers.Translational research : the journal of laboratory and clinical medicine · 2017Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Current atherosclerosis treatment strategies primarily focus on limiting further cholesteryl esters (CE) accumulation by reducing endogenous synthesis of cholesterol in the liver. No therapy is currently available to enhance the removal of CE, a crucial step to reduce the burden of the existing disease. Given the central role of hepatic cholesteryl ester hydrolase (CEH) in the intrahepatic hydrolysis of CE and subsequent removal of the resulting free cholesterol (FC), in this work, we applied galactose-functionalized polyamidoamine (PAMAM) dendrimer generation 5 (Gal-G5) for hepatocyte-specific delivery of CEH expression vector. The data presented herein show the increased specific uptake of Gal-G5/CEH expression vector complexes (simply Gal-G5/CEH) by hepatocytes in vitro and in vivo. Furthermore, the upregulated CEH expression in the hepatocytes significantly enhanced the intracellular hydrolysis of high density lipoprotein-associated CE (HDL-CE) and subsequent conversion/secretion of hydrolyzed FC as bile acids (BA). The increased CEH expression in the liver significantly increased the flux of HDL-CE to biliary as well as fecal FC and BA. Meanwhile, Gal-G5 did not induce hepatic or renal toxicity. It was also not immunotoxic. Because of these encouraging pre-clinical testing results, using this safe and highly efficient hepatocyte-specific gene delivery platform to enhance the hepatic processes involved in cholesterol elimination is a promising strategy for the alleviation of atherosclerosis.
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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.