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Characterization of a novel MR‐detectable nanoantioxidant that mitigates the recall immune response

In many human diseases, the presence of inflammation is associated with an increase in the level of reactive oxygen species (ROS). The resulting state of oxidative stress is highly detrimental and can initiate a cascade of events that ultimately lead to cell death. Thus, many therapeutic attempts ha...

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Autores principales: Inoue, Taeko, Griffin, Deric M., Huq, Redwan, Samuel, Errol L. G., Ruano, Simone H., Stinnett, Gary, Majid, Tabassum J., Beeton, Christine, Tour, James M., Pautler, Robia G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5035207/
https://www.ncbi.nlm.nih.gov/pubmed/27552925
http://dx.doi.org/10.1002/nbm.3565
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author Inoue, Taeko
Griffin, Deric M.
Huq, Redwan
Samuel, Errol L. G.
Ruano, Simone H.
Stinnett, Gary
Majid, Tabassum J.
Beeton, Christine
Tour, James M.
Pautler, Robia G.
author_facet Inoue, Taeko
Griffin, Deric M.
Huq, Redwan
Samuel, Errol L. G.
Ruano, Simone H.
Stinnett, Gary
Majid, Tabassum J.
Beeton, Christine
Tour, James M.
Pautler, Robia G.
author_sort Inoue, Taeko
collection PubMed
description In many human diseases, the presence of inflammation is associated with an increase in the level of reactive oxygen species (ROS). The resulting state of oxidative stress is highly detrimental and can initiate a cascade of events that ultimately lead to cell death. Thus, many therapeutic attempts have been focused on either modulating the immune system to lower inflammation or reducing the damaging caused by ROS. Berlin et al. reported the development of a novel nanoantioxidant known as poly(ethylene glycol)‐functionalized‐hydrophilic carbon clusters (PEG‐HCCs). They showed that PEG‐HCCs could be targeted to cancer cells, utilized as a drug delivery vector, and can even be visualized ex vivo. Our work here furthers this work and characterizes Gd‐DTPA conjugated PEG‐HCCs and explores the potential for in vivo tracking of T cells in live mice. We utilized a mouse model of delayed‐type hypersensitivity (DTH) to assess the immunomodulatory effects of PEG‐HCCs. The T (1)‐agent Gd‐DTPA was then conjugated to the PEG‐HCCs and T (1) measurements, and T (1)‐weighted MRI of the modified PEG‐HCCs was done to assess their relaxivity. We then assessed if PEG‐HCCs could be visualized both ex vivo and in vivo within the mouse lymph node and spleen. Mice treated with PEG‐HCCs showed significant improvements in the DTH assay as compared to the vehicle (saline)‐treated control. Flow cytometry demonstrated that splenic T cells are capable of internalizing PEG‐HCCs whereas fluorescent immunohistochemistry showed that PEG‐HCCs are detectable within the cortex of lymph nodes. Finally, our nanoantioxidants can be visualized in vivo within the lymph nodes and spleen of a mouse after addition of the Gd‐DTPA. PEG‐HCCs are internalized by T cells in the spleen and can reduce inflammation by suppression of a recall immune response. PEG‐HCCs can be modified to allow for both in vitro and in vivo visualization using MRI. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.
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spelling pubmed-50352072016-10-19 Characterization of a novel MR‐detectable nanoantioxidant that mitigates the recall immune response Inoue, Taeko Griffin, Deric M. Huq, Redwan Samuel, Errol L. G. Ruano, Simone H. Stinnett, Gary Majid, Tabassum J. Beeton, Christine Tour, James M. Pautler, Robia G. NMR Biomed Research Articles In many human diseases, the presence of inflammation is associated with an increase in the level of reactive oxygen species (ROS). The resulting state of oxidative stress is highly detrimental and can initiate a cascade of events that ultimately lead to cell death. Thus, many therapeutic attempts have been focused on either modulating the immune system to lower inflammation or reducing the damaging caused by ROS. Berlin et al. reported the development of a novel nanoantioxidant known as poly(ethylene glycol)‐functionalized‐hydrophilic carbon clusters (PEG‐HCCs). They showed that PEG‐HCCs could be targeted to cancer cells, utilized as a drug delivery vector, and can even be visualized ex vivo. Our work here furthers this work and characterizes Gd‐DTPA conjugated PEG‐HCCs and explores the potential for in vivo tracking of T cells in live mice. We utilized a mouse model of delayed‐type hypersensitivity (DTH) to assess the immunomodulatory effects of PEG‐HCCs. The T (1)‐agent Gd‐DTPA was then conjugated to the PEG‐HCCs and T (1) measurements, and T (1)‐weighted MRI of the modified PEG‐HCCs was done to assess their relaxivity. We then assessed if PEG‐HCCs could be visualized both ex vivo and in vivo within the mouse lymph node and spleen. Mice treated with PEG‐HCCs showed significant improvements in the DTH assay as compared to the vehicle (saline)‐treated control. Flow cytometry demonstrated that splenic T cells are capable of internalizing PEG‐HCCs whereas fluorescent immunohistochemistry showed that PEG‐HCCs are detectable within the cortex of lymph nodes. Finally, our nanoantioxidants can be visualized in vivo within the lymph nodes and spleen of a mouse after addition of the Gd‐DTPA. PEG‐HCCs are internalized by T cells in the spleen and can reduce inflammation by suppression of a recall immune response. PEG‐HCCs can be modified to allow for both in vitro and in vivo visualization using MRI. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd. John Wiley and Sons Inc. 2016-08-24 2016-10 /pmc/articles/PMC5035207/ /pubmed/27552925 http://dx.doi.org/10.1002/nbm.3565 Text en © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Inoue, Taeko
Griffin, Deric M.
Huq, Redwan
Samuel, Errol L. G.
Ruano, Simone H.
Stinnett, Gary
Majid, Tabassum J.
Beeton, Christine
Tour, James M.
Pautler, Robia G.
Characterization of a novel MR‐detectable nanoantioxidant that mitigates the recall immune response
title Characterization of a novel MR‐detectable nanoantioxidant that mitigates the recall immune response
title_full Characterization of a novel MR‐detectable nanoantioxidant that mitigates the recall immune response
title_fullStr Characterization of a novel MR‐detectable nanoantioxidant that mitigates the recall immune response
title_full_unstemmed Characterization of a novel MR‐detectable nanoantioxidant that mitigates the recall immune response
title_short Characterization of a novel MR‐detectable nanoantioxidant that mitigates the recall immune response
title_sort characterization of a novel mr‐detectable nanoantioxidant that mitigates the recall immune response
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5035207/
https://www.ncbi.nlm.nih.gov/pubmed/27552925
http://dx.doi.org/10.1002/nbm.3565
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