Browsing by Author "Pautler, Robia G."

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Antioxidant Carbon Particles Improve Cerebrovascular Dysfunction Following Traumatic Brain Injury
    (American Chemical Society, 2012) Bitner, Brittany R.; Marcano, Daniela C.; Berlin, Jacob M.; Fabian, Roderic H.; Cherian, Leela; Culver, James C.; Dickinson, Mary E.; Robertson, Claudia S.; Pautler, Robia G.; Kent, Thomas A.; Tour, James M.; Smalley Institute for Nanoscale Science and Technology
    Injury to the neurovasculature is a feature of brain injury and must be addressed to maximize opportunity for improvement. Cerebrovascular dysfunction, manifested by reduction in cerebral blood flow (CBF), is a key factor that worsens outcome after traumatic brain injury (TBI), most notably under conditions of hypotension. We report here that a new class of antioxidants, poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs), which are nontoxic carbon particles, rapidly restore CBF in a mild TBI/hypotension/resuscitation rat model when administered during resuscitation--a clinically relevant time point. Along with restoration of CBF, there is a concomitant normalization of superoxide and nitric oxide levels. Given the role of poor CBF in determining outcome, this finding is of major importance for improving patient health under clinically relevant conditions during resuscitative care, and it has direct implications for the current TBI/hypotension war-fighter victims in the Afghanistan and Middle East theaters. The results also have relevancy in other related acute circumstances such as stroke and organ transplantation.
  • Thumbnail Image
    Item
    Characterization of a novel MR-detectable nanoantioxidant that mitigates the recall immune response
    (Wiley, 2016) 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.; The NanoCarbon Center
    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 T1-agent Gd-DTPA was then conjugated to the PEG-HCCs and T1 measurements, and T1-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.
  • Thumbnail Image
    Item
    Preferential uptake of antioxidant carbon nanoparticles by T lymphocytes for immunomodulation
    (Springer Nature, 2016) 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; The NanoCarbon Center
    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.
  • Thumbnail Image
    Item
    Targeting pancreatic cancer with magneto-fluorescent theranostic gold nanoshells
    (Future Medicine, 2014) Chen, Wenxue; Ayala-Orozco, Ciceron; Biswal, Nrusingh C.; Perez-Torres, Carlos; Bartels, Marc; Bardhan, Rizia; Stinnet, Gary; Liu, Xian-De; Ji, Baoan; Deorukhkar, Amit; Brown, Lisa V.; Guha, Sushovan; Pautler, Robia G.; Krishnan, Sunil; Halas, Naomi J.; Joshi, Amit
    Aim: We report a magneto-fluorescent theranostic nanocomplex targeted to neutrophil gelatinase-associated lipocalin (NGAL) for imaging and therapy of pancreatic cancer. Materials & methods: Gold nanoshells resonant at 810 nm were encapsulated in silica epilayers doped with iron oxide and the near-infrared (NIR) dye indocyanine green, resulting in theranostic gold nanoshells (TGNS), which were subsequently conjugated with antibodies targeting NGAL in AsPC-1-derived xenografts in nude mice. Results: Anti-NGAL-conjugated TGNS specifically targeted pancreatic cancer cells in vitro and in vivo providing contrast for both NIR fluorescence and T2-weighted MRI with higher tumor contrast than can be obtained using long-circulating, but nontargeted, PEGylated nanoparticles. The nanocomplexes also enabled highly specific cancer cell death via NIR photothermal therapy in vitro. Conclusion: TGNS with embedded NIR and magnetic resonance contrasts can be specifically targeted to pancreatic cancer cells with expression of early disease marker NGAL, and enable molecularly targeted imaging and photothermal therapy.
  • Thumbnail Image
    Item
    Use of carbon nanomaterials with antioxidant properties to treat oxidative stress
    (2017-02-21) Tour, James M.; Berlin, Jacob; Marcano, Daniela; Leonard, Ashley; Kent, Thomas A.; Pautler, Robia G.; Bitner, Brittany; Inoue, Taeko; Rice University; United States Patent and Trademark Office
    In some embodiments, the present invention provides methods of treating oxidative stress in a subject by administering a therapeutic composition to the subject. In some embodiments, the therapeutic composition comprises a carbon nanomaterial with anti-oxidant activity. In some embodiments, the anti-oxidant activity of the carbon nanomaterial corresponds to ORAC values between about 200 to about 15,000. In some embodiments, the administered carbon nanomaterials include at least one of single-walled nanotubes, double-walled nanotubes, triple-walled nanotubes, multi-walled nanotubes, ultra-short nanotubes, graphene, graphene nanoribbons, graphite, graphite oxide nanoribbons, carbon black, oxidized carbon black, hydrophilic carbon clusters, and combinations thereof. In some embodiments, the carbon nanomaterial is an ultra-short single-walled nanotube that is functionalized with a plurality of solubilizing groups. In some embodiments, the carbon nanomaterial is a polyethylene glycol functionalized hydrophilic carbon cluster (PEG-HCC). In some embodiments, the administered therapeutic compositions of the present invention may also include an active agent or targeting agent associated with the carbon nanomaterial. Additional embodiments of the present invention pertain to the aforementioned carbon nanomaterial compositions for treating oxidative stress.