Characterization of a novel MR‐detectable nanoantioxidant that mitigates the recall immune response. (24th August 2016)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: NMR in biomedicine. Volume 29:Number 10(2016:Oct.)
• Page Start: 1436
• Page End: 1444
• Publication Date: 2016-08-24
• Subjects: MRI -- nanotechnology -- oxidative stress -- cell labeling -- T1 agents -- PEG‐HCCs -- antioxidant -- inflammation; Nuclear magnetic resonance -- Periodicals; Magnetic Resonance Spectroscopy -- Periodicals; 574
• DOI: 10.1002/nbm.3565
• Languages: English
• ISSNs: 0952-3480

Abstract

Abstract : 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. Abstract : Splenic T cells take up PEG‐HCCs. As shown in a.), the T cell surface marker CD3 was used to isolate a purified population of T cells from vehicle and PEG‐HCC treated animals. These T cells were then assessed for presence of PEG‐HCCs as shown in b.) Among PEG‐HCC treated samples, permeabilized samples had significantly higher PEG positive cells than what was observed in intact samples. n = 3 per group. * < 0.05.