title: Targeted diazeniumdiolates: localized nitric oxide release from glioma-specific peptides and proteins.
abstract: Nitric oxide (NO) is a small yet important biological messenger, which at sufficient concentrations has been shown to induce apoptosis as well as increase radiosensitization in tumor cells. However, the short half-life of NO gas itself has limited its utility as a therapeutic agent. The objective of this study was the development of targeted NO donors and we illustrate their utility as a potential therapeutic for treatment of glioblastoma multiforme, the most common and aggressive malignant primary brain tumor in adults. We have synthesized two diazeniumdiolate NO donors by reacting NO gas with glioma-specific targeting sequences, VTWTPQAWFQWVGGGSKKKKK (VTW) and chlorotoxin (CTX), and achieved repeatable NO release from both donors. FITC-labeled biomolecules, when incubated with glioma and control cells preferentially bound to the glioma cells and showed only minimal binding to the control cells. Additionally, tumor cell viability was significantly decreased when cells were incubated with the NO donors whereas control cell viability was not affected.
authors.affiliation: School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Dr. NW, Atlanta, GA 30332-0100, United States.
authors.forename: Shahana
authors.initials: S
authors.lastname: Safdar
authors.forename: Lakeshia J
authors.initials: LJ
authors.lastname: Taite
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001391:Azo Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D012604:Scorpion Venoms / Q000737:chemistry / Q000378:metabolism*; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D001391:Azo Compounds; D004337:Drug Carriers; D020030:Nitric Oxide Donors; D009842:Oligopeptides; D012604:Scorpion Venoms; C452539:diazeniumdiolate; C091539:Chlorotoxin; D009569:Nitric Oxide