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Anti-MAdCAM-1-Conjugated Nanocarriers Delivering Quantum Dots Enable Specific Imaging of Inflammatory Bowel Disease
PURPOSE: 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 endotheli...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646444/ https://www.ncbi.nlm.nih.gov/pubmed/33173291 http://dx.doi.org/10.2147/IJN.S264513 |
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author | Truffi, Marta Sevieri, Marta Morelli, Lucia Monieri, Matteo Mazzucchelli, Serena Sorrentino, Luca Allevi, Raffaele Bonizzi, Arianna Zerbi, Pietro Marchini, Beatrice Longhi, Erika Sampietro, Gianluca Matteo Colombo, Francesco Prosperi, Davide Colombo, Miriam Corsi, Fabio |
author_facet | Truffi, Marta Sevieri, Marta Morelli, Lucia Monieri, Matteo Mazzucchelli, Serena Sorrentino, Luca Allevi, Raffaele Bonizzi, Arianna Zerbi, Pietro Marchini, Beatrice Longhi, Erika Sampietro, Gianluca Matteo Colombo, Francesco Prosperi, Davide Colombo, Miriam Corsi, Fabio |
author_sort | Truffi, Marta |
collection | PubMed |
description | PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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. |
format | Online Article Text |
id | pubmed-7646444 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-76464442020-11-09 Anti-MAdCAM-1-Conjugated Nanocarriers Delivering Quantum Dots Enable Specific Imaging of Inflammatory Bowel Disease Truffi, Marta Sevieri, Marta Morelli, Lucia Monieri, Matteo Mazzucchelli, Serena Sorrentino, Luca Allevi, Raffaele Bonizzi, Arianna Zerbi, Pietro Marchini, Beatrice Longhi, Erika Sampietro, Gianluca Matteo Colombo, Francesco Prosperi, Davide Colombo, Miriam Corsi, Fabio Int J Nanomedicine Original Research PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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. Dove 2020-11-02 /pmc/articles/PMC7646444/ /pubmed/33173291 http://dx.doi.org/10.2147/IJN.S264513 Text en © 2020 Truffi et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Truffi, Marta Sevieri, Marta Morelli, Lucia Monieri, Matteo Mazzucchelli, Serena Sorrentino, Luca Allevi, Raffaele Bonizzi, Arianna Zerbi, Pietro Marchini, Beatrice Longhi, Erika Sampietro, Gianluca Matteo Colombo, Francesco Prosperi, Davide Colombo, Miriam Corsi, Fabio Anti-MAdCAM-1-Conjugated Nanocarriers Delivering Quantum Dots Enable Specific Imaging of Inflammatory Bowel Disease |
title | Anti-MAdCAM-1-Conjugated Nanocarriers Delivering Quantum Dots Enable Specific Imaging of Inflammatory Bowel Disease |
title_full | Anti-MAdCAM-1-Conjugated Nanocarriers Delivering Quantum Dots Enable Specific Imaging of Inflammatory Bowel Disease |
title_fullStr | Anti-MAdCAM-1-Conjugated Nanocarriers Delivering Quantum Dots Enable Specific Imaging of Inflammatory Bowel Disease |
title_full_unstemmed | Anti-MAdCAM-1-Conjugated Nanocarriers Delivering Quantum Dots Enable Specific Imaging of Inflammatory Bowel Disease |
title_short | Anti-MAdCAM-1-Conjugated Nanocarriers Delivering Quantum Dots Enable Specific Imaging of Inflammatory Bowel Disease |
title_sort | anti-madcam-1-conjugated nanocarriers delivering quantum dots enable specific imaging of inflammatory bowel disease |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646444/ https://www.ncbi.nlm.nih.gov/pubmed/33173291 http://dx.doi.org/10.2147/IJN.S264513 |
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