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dc.contributor.authorHunt, Nicholas J
dc.contributor.authorLockwood, Glen P
dc.contributor.authorLe Couteur, Frank H.
dc.contributor.authorMcCourt, Peter Anthony
dc.contributor.authorSingla, Nidhi
dc.contributor.authorKang, Sun
dc.contributor.authorBurgess, Andrew
dc.contributor.authorKuncic, Zdenka
dc.contributor.authorLe Couteur, David G
dc.contributor.authorCogger, Victoria C
dc.date.accessioned2022-04-25T12:39:39Z
dc.date.available2022-04-25T12:39:39Z
dc.date.issued2020-01-24
dc.description.abstractQuantum dots (QDs) are used for imaging and transport of therapeutics. Here we demonstrate rapid absorption across the small intestine and targeted delivery of QDs with bound materials to the liver sinusoidal endothelial cells (LSECs) or hepatocytes in vitro and in vivo following oral administration. QDs were radiolabeled with <sup>3</sup> H-oleic acid, with a fluorescent tag or <sup>14</sup>C-metformin placed within a drug binding site. Three different biopolymer shell coatings were compared (formaldehyde-treated serum albumin (FSA), gelatin, heparin). Passage across the small intestine into mesenteric veins is mediated by clathrin endocytosis and micropinocytosis. 60% of an oral dose of QDs was rapidly distributed to the liver within 30 min, and this increased to 85% with FSA biopolymer coating. Uptake into LSECs also increased 3-fold with FSA coating, while uptake into hepatocytes was increased from 40% to 85% with gelatin biopolymer coating. Localization of QDs to LSECs was confirmed with immunofluorescence and transmission electron microscopy. 85% of QDs were cleared within 24 h of administration. The bioavailability of <sup>14</sup>C-metformin 2 h post-ingestion was increased 5-fold by conjugation with QD-FSA, while uptake of metformin into LSECs was improved 50-fold by using these QDs. Endocytosis of QDs by SK-Hep1 cells (an LSEC immortal cell line) was via clathrin- and caveolae-mediated pathways with QDs taken up into lysosomes. In conclusion, we have shown high specificity targeting of the LSEC or hepatocytes after oral administration of QDs coated with a biopolymer layer of FSA or gelatin, which improved the bioavailability and delivery of metformin to LSECs.en_US
dc.identifier.citationHunt NJ, Lockwood GP, Le Couteur F, McCourt PAG, Singla, Kang S, Burgess A, Kuncic, Le Couteur DG, Cogger VC. Rapid Intestinal Uptake and Targeted Delivery to the Liver Endothelium Using Orally Administered Silver Sulfide Quantum Dots.. ACS Nano. 2020;14en_US
dc.identifier.cristinIDFRIDAID 1789956
dc.identifier.doi10.1021/acsnano.9b06071
dc.identifier.issn1936-0851
dc.identifier.issn1936-086X
dc.identifier.urihttps://hdl.handle.net/10037/24879
dc.language.isoengen_US
dc.publisherACS Publicationsen_US
dc.relation.journalACS Nano
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2020 American Chemical Societyen_US
dc.titleRapid Intestinal Uptake and Targeted Delivery to the Liver Endothelium Using Orally Administered Silver Sulfide Quantum Dots.en_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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