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Application Of Nucleic Acid Aptamers XQ-2d In Imaging And Treatment Of Prostate Cancer

Posted on:2021-04-08Degree:MasterType:Thesis
Country:ChinaCandidate:Q HuangFull Text:PDF
GTID:2504306122475244Subject:Chemistry
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In recent years,the incidence of prostate cancer has increased day by day.Prostate cancer has become a major hidden threat to men ’s lives.The detection and treatment of prostate cancer are also becoming more important.Safe and effective detection and treatment methods are the curr ent research hotspots in the field of life sciences.As a molecular recognition tool,nucleic acid aptamers have received extensive attention from researchers because of their high affinity and high specificity,non-immunogenicity,easy chemical modificati on,and wide range of target molecules.Based on the above advantages of nucleic acid aptamers,researchers have developed a variety of intelligent molecular probes and nanowire drug-loading systems,advancing the progress of cancer diagnosis,detection an d treatment technology.However,the absence of specific tumor markers and the interlaced and complex signaling pathways within tumor cells are likely to cause the off-target utility and curative effect of tumor targeting diagnosis and treatment platforms based on antibodies or nucleic acid aptamers.In response to the above problems,we took the prostate cancer cell line DU145 as the research object,based on the nucleic acid aptamer XQ-2d,developed a DNA nanowire drug loading system with adjustable drug ratio and conditional nucleic acid aptamer for the diagnosis and treatment of prostate cancer.The specific content is divided into the following two aspects:In chapter 2: Site-specific modification of paclitaxel(PTX)and c ombretastatin A4(CA4)on DNA hairpins H1 and H2,respectively,to prepare H1-PTX and H2-CA4;then initiate H1-PTX and H2-CA4 by aptamers A hybrid chain reaction occurs to self-assemble to form a DNA nanowire drug-carrying system with a defined drug ratio.We further investigated the ta rgeting performance,endocytosis ability and cytotoxicity of this DNA nanowire drug-loading system in prostate tumor cell DU145,which is expected to provide a new platform for drug synergistic treatment of cancer.In chapter 3: in order to solve the appli cation limitation of the extra-tumor off-target effect of nucleic acid aptamers,we used the hypoxic characteristics of the tumor microenvironment as a prerequisite for the nucleic acid aptamers to exert their recognition capabilities,and developed condit ional nucleic acid aptamer molecular probes,limit the recognition ability of nucleic acid aptamers in tumor microenvironment,thereby reducing the recognition of normal cells by nucleic acid aptamers.Tumor ball model experiments and mouse experiments hav e proved the effectiveness of conditional nucleic acid aptamer molecular probes.This strategy is expected to provide new design ideas for the accurate diagnosis and treatment of malignant tumors.
Keywords/Search Tags:Nucleic acid aptamer, Prostate cancer, Off-target effect, Molecular imaging, Cancer treatment
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