Revisiting nanoparticle transendothelial migration in the liver
Year: 2023
Type: article
Abstract: The approval of Onpattro by the US Food and Drug Administration in 2018 1 Akinc A. Maier M.A. Manoharan M. Fitzgerald K. Jayaraman M. Barros S. Ansell S. Du X. Hope M.J. Madden T.D. et al. The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs. Nat. Nanotechnol. 2019; 14: 1084-1087https://doi.org/10.1038/s41565-019-0591-y Crossref PubMed Scopus (621) Google Scholar has stimulated much interest in lipid nanoparticles (LNPs) with ionisable cationic lipids for the delivery of gene medicines to hepatocytes. While physicochemical aspects of LNP formulations and their intracellular performance have been studied, 1 Akinc A. Maier M.A. Manoharan M. Fitzgerald K. Jayaraman M. Barros S. Ansell S. Du X. Hope M.J. Madden T.D. et al. The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs. Nat. Nanotechnol. 2019; 14: 1084-1087https://doi.org/10.1038/s41565-019-0591-y Crossref PubMed Scopus (621) Google Scholar there are limited studies on pathophysiological and physicochemical factors that modulate transendothelial migration of LNPs and related lipid-based carriers in human liver. Furthermore, LNP potency in the liver of widely used preclinical species such as rats and mice may not necessarily translate to successful clinical practice in humans since there are species and strain/substrain differences in hepatic endothelial/sinusoidal ultrastructure. 2 Snoeys J. Lievens J. Wisse E. Jacobs F. Duimel H. Collen D. Frederik P. De Geest B. Species differences in transgene DNA uptake in hepatocytes after adenoviral transfer correlate with the size of endothelial fenestrae. Gene Ther. 2007; 14: 604-612https://doi.org/10.1038/sj.gt.3302899 Crossref PubMed Scopus (83) Google Scholar ,3 Wisse E. Jacobs F. Topal B. Frederik P. De Geest B. The size of endothelial fenestrae in human liver sinusoids: implications for hepatocyte-directed gene transfer. Gene Ther. 2008; 15: 1193-1199https://doi.org/10.1038/gt.2008.60 Crossref PubMed Scopus (232) Google Scholar Pathophysiological conditions also modulate “liver sieve” performance. 4 Fraser R. Cogger V.C. Dobbs B. Jamieson H. Warren A. Hilmer S.N. Le Couteur D.G. The liver sieve and atherosclerosis. Pathology (Phila.). 2012; 44: 181-186https://doi.org/10.1097/PAT.0b013e328351bcc8 Abstract Full Text PDF Scopus (54) Google Scholar A more fundamental understanding of transendothelial migration of nanoparticles would be extremely useful to facilitate translation of LNPs for human liver gene therapy.
Source: Molecular Therapy
Institutions: University of Colorado Anschutz, Newcastle University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,900
OpenAlex ID: W4319443087