Preferential uptake of antioxidant carbon nanoparticles by T lymphocytes for immunomodulation

• Published in: Scientific reports Vol. 6; no. 1; p. 33808
• Main Authors: Huq, Redwan, Samuel, Errol L. G., Sikkema, William K. A., Nilewski, Lizanne G., Lee, Thomas, Tanner, Mark R., Khan, Fatima S., Porter, Paul C., Tajhya, Rajeev B., Patel, Rutvik S., Inoue, Taeko, Pautler, Robia G., Corry, David B., Tour, James M., Beeton, Christine
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22-09-2016; Nature Publishing Group
• Subjects: 13/106; 13/21; 14/28; 631/250/38; 692/699/249/1313/1666; Animal models; Antigen-presenting cells; Antioxidants; Autoimmune diseases; Carbon; Cell activation; Experimental allergic encephalomyelitis; Humanities and Social Sciences; Hydroxyl radicals; Hypersensitivity; Hypersensitivity (delayed); Immunomodulation; Immunosuppressive agents; Lymphocytes; Lymphocytes T; Macrophages; multidisciplinary; Multiple sclerosis; Nanoparticles; Polyethylene glycol; Reactive oxygen species; Science; Side effects; Spleen; Superoxide; T cell receptors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep33808

Autoimmune diseases mediated by a type of white blood cell—T lymphocytes—are currently treated using mainly broad-spectrum immunosuppressants that can lead to adverse side effects. Antioxidants represent an alternative approach for therapy of autoimmune disorders; however, dietary antioxidants are insufficient to play this role. Antioxidant carbon nanoparticles scavenge reactive oxygen species (ROS) with higher efficacy than dietary and endogenous antioxidants. Furthermore, the affinity of carbon nanoparticles for specific cell types represents an emerging tactic for cell-targeted therapy. Here, we report that nontoxic poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs), known scavengers of the ROS superoxide (O
2
•−
) and hydroxyl radical, are preferentially internalized by T lymphocytes over other splenic immune cells. We use this selectivity to inhibit T cell activation without affecting major functions of macrophages, antigen-presenting cells that are crucial for T cell activation. We also demonstrate the
in vivo
effectiveness of PEG-HCCs in reducing T lymphocyte-mediated inflammation in delayed-type hypersensitivity and in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Our results suggest the preferential targeting of PEG-HCCs to T lymphocytes as a novel approach for T lymphocyte immunomodulation in autoimmune diseases without affecting other immune cells.