Browsing by Author "Marcano, Daniela C."

Now showing 1 - 6 of 6
  • 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
    Chronic exposure to carbon black ultrafine particles reprograms macrophage metabolism and accelerates lung cancer
    (AAAS, 2022) Chang, Cheng-Yen; You, Ran; Armstrong, Dominique; Bandi, Ashwini; Cheng, Yi-Ting; Burkhardt, Philip M.; Becerra-Dominguez, Luis; Madison, Matthew C.; Tung, Hui-Ying; Zeng, Zhimin; Wu, Yifan; Song, Lizhen; Phillips, Patricia E.; Porter, Paul; Knight, John M.; Putluri, Nagireddy; Yuan, Xiaoyi; Marcano, Daniela C.; McHugh, Emily A.; Tour, James M.; Catic, Andre; Maneix, Laure; Burt, Bryan M.; Lee, Hyun-Sung; Corry, David B.; Kheradmand, Farrah
    Chronic exposure to airborne carbon black ultrafine (nCB) particles generated from incomplete combustion of organic matter drives IL-17A–dependent emphysema. However, whether and how they alter the immune responses to lung cancer remains unknown. Here, we show that exposure to nCB particles increased PD-L1+ PD-L2+ CD206+ antigen-presenting cells (APCs), exhausted T cells, and Treg cells. Lung macrophages that harbored nCB particles showed selective mitochondrial structure damage and decreased oxidative respiration. Lung macrophages sustained the HIF1α axis that increased glycolysis and lactate production, culminating in an immunosuppressive microenvironment in multiple mouse models of non–small cell lung cancers. Adoptive transfer of lung APCs from nCB-exposed wild type to susceptible mice increased tumor incidence and caused early metastasis. Our findings show that nCB exposure metabolically rewires lung macrophages to promote immunosuppression and accelerates the development of lung cancer.
  • Thumbnail Image
    Item
    Hydrophilic carbon clusters as therapeutic, high-capacity antioxidants
    (Elsevier, 2014) Samuel, Errol L.G.; Duong, MyLinh T.; Bitner, Brittany R.; Marcano, Daniela C.; Tour, James M.; Kent, Thomas A.; Smalley Institute for Nanoscale Science and Technology
    Oxidative stress reflects an excessive accumulation of reactive oxygen species (ROS) and is a hallmark of several acute and chronic human pathologies. Although many antioxidants have been investigated, most have demonstrated poor efficacy in clinical trials. Here we discuss the limitations of current antioxidants and describe a new class of nanoparticle antioxidants, poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs). PEG-HCCs show high capacity to annihilate ROS such as superoxide (O2(•-)) and the hydroxyl (HO(•)) radical, show no reactivity toward the nitric oxide radical (NO(•)), and can be functionalized with targeting moieties without loss of activity. Given these properties, we propose that PEG-HCCs offer an exciting new area of study for the treatment of numerous ROS-induced human pathologies..
  • Thumbnail Image
    Item
    The microRNA miR-22 inhibits the histone deacetylase HDAC4 to promote TH17 cell–dependent emphysema
    (Nature Publishing Group, 2015) Lu, Wen; You, Ran; Yuan, Xiaoyi; Yang, Tianshu; Samuel, Errol L.G.; Marcano, Daniela C.; Sikkema, William K.A.; Tour, James M.; Rodriguez, Antony; Kheradmand, Farrah; Corry, David B.
    Smoking-related emphysema is a chronic inflammatory disease driven by the T(H)17 subset of helper T cells through molecular mechanisms that remain obscure. Here we explored the role of the microRNA miR-22 in emphysema. We found that miR-22 was upregulated in lung myeloid dendritic cells (mDCs) of smokers with emphysema and antigen-presenting cells (APCs) of mice exposed to smoke or nanoparticulate carbon black (nCB) through a mechanism that involved the transcription factor NF-κB. Mice deficient in miR-22, but not wild-type mice, showed attenuated T(H)17 responses and failed to develop emphysema after exposure to smoke or nCB. We further found that miR-22 controlled the activation of APCs and T(H)17 responses through the activation of AP-1 transcription factor complexes and the histone deacetylase HDAC4. Thus, miR-22 is a critical regulator of both emphysema and T(H)17 responses.
  • Thumbnail Image
    Item
    Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17-mediated emphysema
    (eLife Sciences Publications Ltd., 2015) You, Ran; Lu, Wen; Shan, Ming; Berlin, Jacob M.; Samuel, Errol L.G.; Marcano, Daniela C.; Sun, Zhengzong; Sikkema, William K.A.; Yuan, Xiaoyi; Song, Lizhen; Hendrix, Amanda Y.; Tour, James M.; Corry, David B.; Kheradmand, Farrah
    Chronic inhalation of cigarette smoke is the major cause of sterile inflammation and pulmonary emphysema. The effect of carbon black (CB), a universal constituent of smoke derived from the incomplete combustion of organic material, in smokers and non-smokers is less known. In this study, we show that insoluble nanoparticulate carbon black (nCB) accumulates in human myeloid dendritic cells (mDCs) from emphysematous lung and in CD11c+ lung antigen presenting cells (APC) of mice exposed to smoke. Likewise, nCB intranasal administration induced emphysema in mouse lungs. Delivered by smoking or intranasally, nCB persisted indefinitely in mouse lung, activated lung APCs, and promoted T helper 17 cell differentiation through double-stranded DNA break (DSB) and ASC-mediated inflammasome assembly in phagocytes. Increasing the polarity or size of CB mitigated many adverse effects. Thus, nCB causes sterile inflammation, DSB, and emphysema and explains adverse health outcomes seen in smokers while implicating the dangers of nCB exposure in non-smokers.
  • Thumbnail Image
    Item
    Noncovalent Assembly of Targeted Carbon Nanovectors Enables Synergistic Drug and Radiation Cancer Therapyﾠin Vivo
    (American Chemical Society, 2012) Sano, Daisuke; Berlin, Jacob M.; Pham, Tam T.; Marcano, Daniela C.; Valdecanas, David R.; Zhou, Ge; Milas, Luka; Myers, Jeffrey N.; Tour, James M.; Smalley Institute for Nanoscale Science and Technology
    Current chemotherapeutics are characterized by efficient tumor cell-killing and severe side effects mostly derived from off-target toxicity. Hence targeted delivery of these drugs to tumor cells is actively sought. In anﾠin vitroﾠsystem, we previously demonstrated that targeted drug delivery to cancer cells overexpressing epidermal growth factor receptor (EGFR+) can be achieved by poly(ethylene glycol)-functionalized carbon nanovectors simply mixed with a drug, paclitaxel, and an antibody that binds to the epidermal growth factor receptor, cetuximab. This construct is unusual in that all three components are assembled through noncovalent interactions. Here we show that this same construct is effectiveﾠin vivo, enhancing radiotherapy of EGFR+ tumors. This targeted nanovector system has the potential to be a new therapy for head and neck squamous cell carcinomas, deserving of further preclinical development.