Design of poly(ethylene glycol)-functionalized hydrophilic carbon clusters for targeted therapy of cerebrovascular dysfunction in mild traumatic brain injury

Daniela C. Marcano, Brittany R. Bitner, Jacob M. Berlin, Jane Jarjour, Juhye M. Lee, Aakash Jacob, Roderic H. Fabian, Thomas A. Kent, James M. Tour

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Traumatic brain injury (TBI) involves the elaboration of oxidative stress that causes cerebrovascular dysfunction, including impairment of autoregulation of cerebral blood flow. Currently, there is no clinically effective antioxidant treatment for these pathologies. Most currently available antioxidants act through mechanisms in which the antioxidant either transfers the radical or requires regeneration, both of which are impaired in the toxic post-TBI environment. We previously reported that single-walled carbon nanotubes (SWCNTs) and ultrashort SWCNTs possess antioxidant activity, and their characteristics suggest that radical annihilation is the major mechanism. We have now developed a biologically compatible class of carbon-based nanovectors, poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs) that can be further functionalized with antibodies, and hence show promise as targeted drug delivery platforms. Here we report that PEG-HCCs possess innate antioxidant activity and can be rapidly targeted via an antibody to the P-selectin antigen in a model of injured cultured brain endothelial cells. One immediate application of this therapy is to vascular dysfunction that accompanies TBI and worsens outcome in the face of systemic hypotension. These in vitro results support the need for further investigation in animal models.

Original languageEnglish (US)
Pages (from-to)789-796
Number of pages8
JournalJournal of Neurotrauma
Volume30
Issue number9
DOIs
StatePublished - May 1 2013

Keywords

  • Antioxidants
  • In vitro
  • P-selectin
  • Targeted drug delivery
  • Vascular dysfunction
  • mildTBI

ASJC Scopus subject areas

  • Clinical Neurology

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