Tolerogenic Iron Oxide Nanoparticles in Type 1 Diabetes: Biodistribution and Pharmacokinetics Studies in Nonobese Diabetic Mice

Tolerogenic Iron Oxide Nanoparticles in Type 1 Diabetes: Biodistribution and Pharmacokinetics Studies in Nonobese Diabetic Mice

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...

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Published in:Small (Weinheim an der Bergstrasse, Germany) Vol. 14; no. 40; pp. e1802053 - n/a
Main Authors: Dubreil, Chloe, Sainte Catherine, Odile, Lalatonne, Yoann, Journé, Clément, Ou, Phalla, van Endert, Peter, Motte, Laurence
Format: Journal Article
Language:English
Published: Germany Wiley Subscription Services, Inc 01-10-2018
Subjects:
Accumulation
biodistribution
Carbonyls
Contrast agents
copackaging
Diabetes
Diabetes mellitus
diagnosis
Immunity
iron oxide nanoparticles
Iron oxides
Kidneys
Liver
Magnetic resonance imaging
Medical imaging
Mice
Nanoparticles
Nanotechnology
NMR
Nuclear magnetic resonance
Organs
Pancreas
pharmacokinetic
Pharmacokinetics
Pharmacology
Rodents
type 1 diabetes
diagnosis
biodistribution
type 1 diabetes
pharmacokinetic
copackaging
iron oxide nanoparticles
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Summary: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. Iron oxide nanoparticles are surface‐engineered for the copackaging of the autoantigen proinsulin, a target of adaptive immunity in type 1 diabetes (T1D), and a small drug conditioning a tolerogenic environment. These nanoparticles accumulate in the pancreas of prediabetic mice and are potential magnetic resonance imaging contrast agents for early T1D diagnosis. 24 h after i.v. injection, the nanoparticles recirculate.
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ISSN:1613-6810
1613-6829
DOI:10.1002/smll.201802053