The Detection Of MicroRNA And Diagnosis-treatment Based On Functional Logic Gate And Dual-mode DNA Signal Amplification Probe

Biotechnology for diagnosis and treatment of critical illnesses has increasingly become the focus of research in the field of biomedicine.The integration of diagnosis and treatment through a rational design and synthesis of two separate processes of diagnosis and treatment in one nanocarrier is the integration of diagnosis and treatment.Its main function is to integrate fast real-time diagnosis and specific targeted treatment.It is extremely important to design a novel,efficient and safe multifunctional diagnosis and treatment integrated nano-platform for early diagnosis and treatment of diseases.In this research project,the advantages of fluorescence and surface enhanced Raman spectroscopy(SERS)are used to construct a functional dual-input signal amplification logic gate,which can realize sensitive detection of multiple microRNAs(miRNA).On the basis of this research,a multifunctional dual-mode DNA robot enhanced diagnostic therapy probe was designed to catalyze the amplification reaction of intracellular circulation by endogenous substances to achieve accurate detection of miRNA and fluorescence imaging-guided chemical-gene comprehensive enhanced targeted therapy.This research paper is developed from the following two aspects:(1)Constructed a functionalized dual-input signal amplification logic gate.Using magnetic nanoparticles(MBs)and gold nanoparticles as carriers to modify functionalized DNA molecules,by introducing different hairpin structures and two types of signal molecules modified DNA chains,combined with the advantages of hybrid chain reaction(HCR)to design A dual-input DNA logic gate for signal amplification.Grasp the amplified SERS signal as output,realize a series of complex logic operations,and realize the signal expansion of multiple miRNA detection.XOR logic gates were extended to detect miR-21 and let-7a and AND,OR two-step logic gates used to detect miR-21 and miR-206.This work may provide a powerful tool for the sensitive detection of multiple miRNAs and stimulate the further development of the functionalization of DNA logic gates.(2)Designed a multifunctional dual-mode DNA robot enhanced diagnosis and treatment probe(DDR probe).Combining the complementary advantages of fluorescence and surface enhanced Raman spectroscopy(SERS)technology,when the DDR probe enters the cell,it specifically recognizes miR-21 and is catalyzed by the intracellular ATP molecule,which triggers hybridization to initiate a foothold chain replacement reaction(TSDR),Making the functional DNA assembled with AuNPs form a unique 3D nano plasma structure,generating SERS hotspot effect,enhancing SERS signal,and achieving sensitive and efficient detection of miR-21 in cells.At the same time,the drug is released and the nucleic acid molecule targeted for inhibition is released to realize fluorescent imaging-guided chemical-gene enhanced targeted therapy,and a significant tumor suppression effect is achieved by initiating various anti-tumor mechanisms.