Tolerogenic Iron Oxide Nanoparticles in Type 1 Diabetes: Biodistribution and Pharmacokinetics Studies in Nonobese Diabetic Mice
| Autor: | Clément Journé, Chloe Dubreil, Yoann Lalatonne, Odile Sainte Catherine, Phalla Ou, Laurence Motte, Peter van Endert |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Biodistribution Indoles Contrast Media 02 engineering and technology Nod Pharmacology Kidney Ferric Compounds Diabetes Mellitus Experimental Biomaterials Diabetic nephropathy Mice 03 medical and health sciences Pharmacokinetics Mice Inbred NOD medicine Animals General Materials Science Pancreas Proinsulin NOD mice Chemistry General Chemistry 021001 nanoscience & nanotechnology medicine.disease Magnetic Resonance Imaging Thiazoles Diabetes Mellitus Type 1 030104 developmental biology medicine.anatomical_structure Liver Nanoparticles 0210 nano-technology Biotechnology |
| Zdroj: | Small. 14:1802053 |
| ISSN: | 1613-6810 |
| Popis: | Nanoparticle (NP) administration is among the most attractive approaches to exploit the synergy of different copackaged molecules for the same target. In this work, iron oxide NPs are surface-engineered for the copackaging of the autoantigen proinsulin, a major target of adaptive immunity in type 1 diabetes (T1D), and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methylester (ITE), a small drug conditioning a tolerogenic environment. Magnetic resonance imaging (MRI) combined with magnetic quantification are used to investigate NP biokinetics in nonobese diabetic (NOD) mice and control mice in different organs. Different NP biodistribution, with in particular enhanced kidney elimination and a stronger accumulation in the pancreas for prediabetic NOD mice, is observed. This is related to preferential NP accumulation in the pancreatic inflammatory zone and to enhancement of renal elimination by diabetic nephropathy. For both mouse strains, an MRI T2 contrast enhancement at 72 h in the liver, pancreas, and kidneys, and indicating recirculating NPs, is also found. This unexpected result is confirmed by magnetic quantification at different time points as well as by histological evaluation. Besides, such NPs are potential MRI contrast agents for early diagnosis of T1D. |
| Databáze: | OpenAIRE |
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