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New methods of countering the mechanisms that confer chemoresistance to malignant gliomas could lead to significant advances in the quest to identify novel drug combinations or targeted drug delivery systems for cancer therapy. In this study, we investigate the use of a targeted nitric oxide (NO) donor as a pretreatment to sensitize glioma cells to chemotherapy. The protein chlorotoxin (CTX) has been shown to preferentially target glioma cells, and we have developed CTX\u2013NO, a glioma\u2010specific, NO\u2010donating CTX derivative. Pretreatment of cells with CTX\u2013NO followed by 48\u2010h exposure to either carmustine (BCNU) or temozolomide (TMZ), both common chemotherapeutics used in glioma treatment, resulted in increased efficacy of both therapeutics. After CTX\u2013NO exposure, both T98G and U\u201087MG human malignant glioma cells show increased sensitivity to BCNU and TMZ. Further investigation revealed that the consequences of this combination therapy was a reduction in active levels of the cytoprotective enzyme MGMT and altered p53 activity, both of which are essential in DNA repair and tumor cell resistance to chemotherapy. The combination of CTX\u2013NO and chemotherapeutics also led to decreased cell invasion. These studies indicate that this targeted NO donor could be an invaluable tool in the development of novel approaches to treat cancer. Biotechnol. Bioeng. 2013; 110: 1211\u20131220.  \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/bit.24775","type":"journal-article","created":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T10:42:05Z","timestamp":1351766525000},"page":"1211-1220","source":"Crossref","is-referenced-by-count":24,"title":["Targeted nitric oxide delivery preferentially induces glioma cell chemosensitivity via altered p53 and O<sup>6<\/sup>\u2010Methylguanine\u2010DNA Methyltransferase activity"],"prefix":"10.1002","volume":"110","author":[{"given":"Shahana","family":"Safdar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney A.","family":"Payne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nam H.","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakeshia 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