Abstract
Better understanding the drug action within cells may extend our knowledge on drug action mechanisms and promote new drugs discovery. Herein, we studied the processes of drug induced chemical changes on proteins and nucleic acids in human breast adenocarcinoma (MCF-7) cells via time-resolved plasmonic-enhanced Raman spectroscopy (PERS) in combination with principal component analysis (PCA). Using three popular chemotherapy drugs (fluorouracil, cisplatin and camptothecin) as models, chemical changes during drug action process were clearly discriminated. Reaction kinetics related to protein denaturation, conformational modification, DNA damage and their associated biomolecular events were calculated. Through rate constants and reaction delay times, the different action modes of these drugs could be distinguished. These results may provide vital insights into understanding the chemical reactions associated with drug-cell interactions.
Highlights
Revealing molecular mechanisms of anticancer drugs is one of the most important tasks for drug research[1,2,3]
Choosing three types of commonly-used “nucleus-target” chemotherapy drugs (5-FU, CisPt and CAMP) as models, we studied the processes of drug induced chemical changes on proteins and nucleic acids via time-resolved plasmonic-enhanced Raman spectroscopy (PERS)
The presence of NT-AuNSs enhanced the Raman signals of cells for ~105 folds, but none of the Raman bands of NT-AuNSs appeared as strong bands in the final cell PERS spectra (Fig. 1E)
Summary
Revealing molecular mechanisms of anticancer drugs is one of the most important tasks for drug research[1,2,3]. Drug action on intracellular biomolecules (e.g. protein, DNA, RNA etc.) involve multiple chemical reactions, including bond breakage, conformational modification, native structures degradation and so on[8,9,10]. Finding out how these chemical reactions occurred, and understanding their reaction kinetics would provide extremely valuable information about drug interaction with cells. By fitting the dynamic changes of Raman bands with kinetic model, the rate constants and reaction delay times of protein denaturation, conformational modification, DNA damage and their associated biomolecular events were calculated, by which the difference on action modes of these three types of drugs could be distinguished
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