Anti-MAdCAM-1-Conjugated Nanocarriers Delivering Quantum Dots Enable Specific Imaging of Inflammatory Bowel Disease.
Animals
Antibodies, Monoclonal
/ chemistry
Cell Adhesion Molecules
/ immunology
Colitis
/ chemically induced
Crohn Disease
/ diagnostic imaging
Disease Models, Animal
Female
Humans
Immunoconjugates
/ administration & dosage
Inflammatory Bowel Diseases
/ diagnostic imaging
Injections, Intravenous
Intestinal Mucosa
/ diagnostic imaging
Intestines
/ diagnostic imaging
Magnetic Resonance Imaging
/ methods
Mice, Inbred C57BL
Mucoproteins
/ immunology
Nanoparticles
/ administration & dosage
Polyesters
/ chemistry
Polyethylene Glycols
/ chemistry
Quantum Dots
/ administration & dosage
Tissue Distribution
adhesion molecule
inflamed bowel
polymeric nanoparticles
targeted imaging
Journal
International journal of nanomedicine
ISSN: 1178-2013
Titre abrégé: Int J Nanomedicine
Pays: New Zealand
ID NLM: 101263847
Informations de publication
Date de publication:
2020
2020
Historique:
received:
25
06
2020
accepted:
01
09
2020
entrez:
11
11
2020
pubmed:
12
11
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Assessment of inflammatory bowel disease (IBD) currently relies on aspecific clinical signs of bowel inflammation. Specific imaging of the diseased bowel regions is still lacking. Here, we investigate mucosal addressin cell adhesion molecule 1 (MAdCAM-1) as a reliable and specific endothelial target for engineered nanoparticles delivering imaging agents to obtain an exact mapping of diseased bowel foci. We generated a nanodevice composed of PLGA-PEG coupled with anti-MAdCAM-1 antibody half-chains and loaded with quantum dots (P@QD-MdC NPs). Bowel localization and systemic biodistribution of the nanoconjugate were analyzed upon injection in a murine model of chronic IBD obtained through repeated administration of dextran sulfate sodium salt. Specificity for diseased bowel regions was also assessed ex vivo in human specimens from patients with IBD. Potential for development as contrast agent in magnetic resonance imaging was assessed by preliminary study on animal model. Synthesized nanoparticles revealed good stability and monodispersity. Molecular targeting properties were analyzed in vitro in a cell culture model. Upon intravenous injection, P@QD-MdC NPs were localized in the bowel of colitic mice, with enhanced accumulation at 24 h post-injection compared to untargeted nanoparticles (p<0.05). Nanoparticles injection did not induce histologic lesions in non-target organs. Ex vivo exposure of human bowel specimens to P@QD-MdC NPs revealed specific recognition of the diseased regions vs uninvolved tracts (p<0.0001). After loading with appropriate contrast agent, the nanoparticles enabled localized contrast enhancement of bowel mucosa in the rectum of treated mice. P@QD-MdC NPs efficiently detected bowel inflammation foci, accurately following the expression pattern of MAdCAM-1. Fine-tuning of this nanoconjugate with appropriate imaging agents offers a promising non-invasive tool for specific IBD diagnosis.
Identifiants
pubmed: 33173291
doi: 10.2147/IJN.S264513
pii: 264513
pmc: PMC7646444
doi:
Substances chimiques
Antibodies, Monoclonal
0
Cell Adhesion Molecules
0
Immunoconjugates
0
MADCAM1 protein, human
0
Mucoproteins
0
Polyesters
0
polyethylene glycol-poly(lactide-co-glycolide)
0
Polyethylene Glycols
3WJQ0SDW1A
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8537-8552Informations de copyright
© 2020 Truffi et al.
Déclaration de conflit d'intérêts
The authors have no conflict of interest to declare regarding this study.
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