• Rapid Intestinal Uptake and Targeted Delivery to the Liver Endothelium Using Orally Administered Silver Sulfide Quantum Dots.

Rapid Intestinal Uptake and Targeted Delivery to the Liver Endothelium Using Orally Administered Silver Sulfide Quantum Dots.

ACS nano (2020-01-25)
Nicholas J Hunt, Glen P Lockwood, Frank H Le Couteur, Peter A G McCourt, Nidhi Singla, Sun Woo Sophie Kang, Andrew Burgess, Zdenka Kuncic, David G Le Couteur, Victoria C Cogger

Quantum 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 3H-oleic acid, with a fluorescent tag or 14C-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 14C-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.

Product Number
Product Description

N-Hydroxysulfosuccinimide sodium salt, ≥98% (HPLC)
N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, crystalline
Epoxy Embedding Medium kit, embedding resin for electron microscopy
Ponceau S solution, BioReagent, suitable (for use in cellulose acetate electrophoresis), 0.1 % (w/v) in 5% acetic acid
Phosphate buffered saline, tablet
TWEEN® 20, viscous liquid
bisBenzimide H 33342 trihydrochloride, for fluorescence, ≥97.0% (HPLC)