Employing chromatographic and spectroscopic methodologies to monitor DNA response to platinum-based chemotherapeutic drugs
In order to design platinum-based chemotherapeutic drugs that express low toxicity and high efficiency, their nature of interaction with DNA, effectiveness, as well as their mechanisms need to be better understood. This research investigates how Cisplatin, cis-diamminedichloroplatinum (II) and its derivatives, Carboplatin, Nedaplatin, and Oxaliplatin, effect DNA stability and structure. Two sensitive and selective analytical methodologies - Surface-Enhanced Raman Scattering (SERS) and High-Performance Liquid Chromatography (HPLC)- were applied to monitor the key concepts stated above. In this project, it was found that of all the drugs, Carboplatin did not significantly modify the DNA. Even though Carboplatin complexes were made at a 1:2 volume ratio it left more DNA unbound (5% unbound) compared to the other drug complexes which were ran at a 1:1 ratio (<2% unbound). Averaging the drug interactions, Cisplatin and Oxaliplatin left less DNA unbound than Nedaplatin did, but Carboplatin in all HPLC experiments left significantly more DNA unbound. In both SERS and HPLC experiments, Carboplatin modified each DNA less than Cisplatin.