Browsing by Author "Berlin, Jacob M."

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    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.
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    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.
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    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.