The Mechanism Of Doxorubicin Interaction With DNA Studied By Laser Confocal Raman Spectroscopy

DNA molecules are the target molecules of many drugs to prevent and treat cancer.Studying the interaction sites and process of action between anti-cancer drugs and DNA molecules is of great significance for elaborating the anti-cancer activity and drug toxicity mechanism,finding low-toxic and efficient anti-cancer drugs,guiding rational drug use and preventing drug pollution.Doxorubicin（DOX）is a broad spectrum anthraquinone anticancer drug with DNA as the target molecule,which has significant therapeutic effects on breast cancer,lung cancer,multiple myeloma and other cancers.However,DOX is severely limited in clinical application due to its cardiotoxicity,gastrointestinal toxicity,dermal toxicity,and other side effects.It is of great significance to clarify the interaction sites and process of DOX and DNA for the study of reducing the toxic and side effects of DOX.Meanwhile,it provides a new idea for the design of drug delivery system of hybrid nanomaterials based on DNA architecture.In this thesis,the interaction sites and process between DOX and DNA are studied,and the research content is summarized as follows:Based on the Laser confocal Raman spectroscopy,the interaction between DOX and calfthymus DNA（ct-DNA）has been systemically investigated.By comparing the Raman spectra of ct-DNA and DOX-DNA complexes,it was found that:The characteristic peaks representing adenine,thymine,cytosine,guanine,and phosphate have red or blue shift,indicating that DOX can interact with the four bases and the phosphate of DNA.Furthermore,the interaction sites of between DOX and DNA were verified by analyzing the Raman spectra of DOX derivatives daunorubicin（DAU）,epirubicin（EPI）,and DAU-DNA,EPI-DNA complexes.Moreover,due to differences in the molecular structure of DAU,EPI,and DOX,the Raman spectra of the DAU-DNA,EPI-DNA,and DOX-DNA complexes have different numbers of red-shift at 1624 cm^-1.Laser confocal Raman spectroscopy technology is used to detect the Raman spectra of DOX-DNA complex in different incubation time periods,and through the analysis of Raman spectra,it is found that the interaction between DOX and DNA molecules is a dynamic process,and the Raman intensity representing the characteristic peaks of adenine,cytosine,phosphoric acid,and deoxyribose will change regularly with the different incubation time.In addition,ultraviolet-visible spectrophotometry was used to support the process of action between DOX and DNA.Finally,a model of DOX and DNA molecules interaction is proposed,that is,there are two modes of action between DOX and DNA molecules,that is,DOX and DNA act to form DOX-DNA complexes,or DOX and DOX act to form multimers,the former compresses DNA molecules,and the latter decompresses the DNA molecules.The competition between these two mechanisms makes the interaction between DOX and DNA more complicated.