title: Insulin-coated gold nanoparticles as a new concept for personalized and adjustable glucose regulation.
abstract: Diabetes mellitus is a chronic metabolic disease, characterized by high blood glucose levels, affecting millions of people around the world. Currently, the main treatment for diabetes requires multiple daily injections of insulin and self-monitoring of blood glucose levels, which markedly affect patients' quality of life. In this study we present a novel strategy for controlled and prolonged glucose regulation, based on the administration of insulin-coated gold nanoparticles (INS-GNPs). We show that both intravenous and subcutaneous injection of INS-GNPs into a mouse model of type 1 diabetes decreases blood glucose levels for periods over 3 times longer than free insulin. We further showed that conjugation of insulin to GNPs prevented its rapid degradation by the insulin-degrading-enzyme, and thus allows controlled and adjustable bio-activity. Moreover, we assessed different sizes and concentrations of INS-GNPs, and found that both parameters have a critical effect in vivo, enabling specific adjustment of blood glucose levels. These findings have the potential to improve patient compliance in diabetes mellitus.
authors.affiliation: Faculty of Engineering & Institutes of Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat-Gan, 5290002, Israel. rachela.popovtzer@biu.ac.il.
authors.forename: Malka
authors.initials: M
authors.lastname: Shilo
authors.affiliation: Everard and Mina Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
authors.forename: Peter
authors.initials: P
authors.lastname: Berenstein
authors.affiliation: Faculty of Engineering & Institutes of Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat-Gan, 5290002, Israel. rachela.popovtzer@biu.ac.il.
authors.forename: Tamar
authors.initials: T
authors.lastname: Dreifuss
authors.affiliation: Department of Neurobiology & Sagol School for Neuroscience, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 6997801 Israel and Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 6997801 Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Nash
authors.affiliation: Department of Neurobiology & Sagol School for Neuroscience, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 6997801 Israel.
authors.forename: Guy
authors.initials: G
authors.lastname: Goldsmith
authors.affiliation: Everard and Mina Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
authors.forename: Gila
authors.initials: G
authors.lastname: Kazimirsky
authors.affiliation: Faculty of Engineering & Institutes of Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat-Gan, 5290002, Israel. rachela.popovtzer@biu.ac.il.
authors.forename: Menachem
authors.initials: M
authors.lastname: Motiei
authors.affiliation: Department of Neurobiology & Sagol School for Neuroscience, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 6997801 Israel and Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 6997801 Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Frenkel
authors.affiliation: Everard and Mina Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
authors.forename: Chaya
authors.initials: C
authors.lastname: Brodie
authors.affiliation: Faculty of Engineering & Institutes of Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat-Gan, 5290002, Israel. rachela.popovtzer@biu.ac.il.
authors.forename: Rachela
authors.initials: R
authors.lastname: Popovtzer
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy; D006046:Gold / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology; D007328:Insulin / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D016688:Mice, Inbred NOD
chemical_list: D001786:Blood Glucose; D020099:Coated Materials, Biocompatible; D007004:Hypoglycemic Agents; D007328:Insulin; D006046:Gold