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Detection Of RNA And Cancer Therapy Based On Nucleic Acid Technology

Posted on:2021-04-05Degree:MasterType:Thesis
Country:ChinaCandidate:Z H ZhangFull Text:PDF
GTID:2404330611488158Subject:Analytical Chemistry
Abstract/Summary:PDF Full Text Request
Cancer is one of the greatest risk to human health.The rate of cancer is a long process and the cause is complicated.There are many risk factors and long course of this disease.However,more than 30%of cancer can be cured by early finding,early diagnosis and early treatment.The patients with advanced cancer could prolong survival time through surgery treatment and chemotherapy.In this paper,a photochemical biosensor was proposed to ultrasensitively and high selectively detect of miRNA141,which combined with DNA Walker,enzyme cycle amplification and cation exchange.To achieve a targeted cancer therapy,a DNA nanohydrogels were constructed as effective targeted inside the tumor cell.After endocytosis by tumor cells and being exposed to the acidic environment,the cascade catalytic reaction was triggered by the released GOx and ferrocene.Therefore,the Fenton and starvation therapies were combined to enhance tumor ablation.The main research content was described as follows:?1?A novel photochemical biosensor was proposed for ultrasensitive detection of miRNA141 with“on-off”strategy,which combined DNA signal amplification and cation exchange reaction.A 3D DNA walker was constructed by using AuNPs and DNA strands.In the presence of target miRNA141,the DNA walker was triggered by base complementation and nicking endonuclease specific cleaving.The target was converted to the intermediate DNA.Then,the intermediate DNA was transformed into numerous Ag+after enzyme cleaving and acidization.The cation exchange reaction was occurred between the Ag+and CdSe QDs,which weakened the photochemical signal.The miRNA141 could be quantitative analysis by the change of photocurrent.The CdSe QDs/TiO2 composites are used to enhance the photocurrent.The proposed strategy exhibits an excellent specificity and sensitivity,which demonstrates potential application in nucleic acid analysis.?2?The functionalized DNA nanohydrogels were constructed for effective targeted cancer therapy.X-shaped monomer was synthesized by base complementation.Based on i-motif sequence,the DNA linker was designed with C–rich sequence and modified with ferrocene in the end.Consequently,the glucose oxidase?GOx?is encapsulated in hydrogel.After modified with AS1411 aptamer,the functionalized DNA nanohydrogels were colonized in the tumor cell and avoided the normal cell.Upon being exposed to the acidic environment,the conformation of i-motif strand was changed to C-quadruplex.Accordingly,GOx is released and catalyze glucose to generate H2O2 with cancer starvation.The elevated H2O2 can be further consumed by Fc via Fenton reaction with resulting much more cytotoxic·OH,inducing tumor cells apoptosis and death.This study provides a new strategy for nanocarrier application in tumor therapy.
Keywords/Search Tags:Photoelectrochemical sensor, DNA Walker, Cation exchange, Hydrogel, Starvation therapy, Fenton reaction
PDF Full Text Request
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