title: Preferential uptake of antioxidant carbon nanoparticles by T lymphocytes for immunomodulation.
abstract: 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 (O2•-) 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.
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.|Graduate Program in Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Redwan
authors.initials: R
authors.lastname: Huq
authors.affiliation: Department of Chemistry, Rice University, Houston, Texas 77005, USA.
authors.forename: Errol L G
authors.initials: EL
authors.lastname: Samuel
authors.affiliation: Department of Chemistry, Rice University, Houston, Texas 77005, USA.
authors.forename: William K A
authors.initials: WK
authors.lastname: Sikkema
authors.affiliation: Department of Chemistry, Rice University, Houston, Texas 77005, USA.
authors.forename: Lizanne G
authors.initials: LG
authors.lastname: Nilewski
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.|Graduate Program in Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lee
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.|Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Tanner
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Fatima S
authors.initials: FS
authors.lastname: Khan
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Porter
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.|Graduate Program in Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Rajeev B
authors.initials: RB
authors.lastname: Tajhya
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Rutvik S
authors.initials: RS
authors.lastname: Patel
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.|Graduate Program in Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Taeko
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Robia G
authors.initials: RG
authors.lastname: Pautler
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.|Biology of Inflammation Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Corry
authors.affiliation: Department of Chemistry, Rice University, Houston, Texas 77005, USA.|The NanoCarbon Center, Rice University, Houston, Texas 77005, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Tour
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.|Biology of Inflammation Center, Baylor College of Medicine, Houston, Texas 77030, USA.|Center for Drug Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Beeton