Construction And Research Of Multi-functional MicroRNA Theranostic Nanoplatforms

MicroRNA(miRNA)plays an important regulatory role in life processes,especially tumorigenesis.Therefore,miRNA can be used as an effective biomarker for cancer diagnosis and prediction.MiRNA detection is a key technology for biological function research,disease diagnosis and development of gene-related drugs.However,due to its short sequence,high familly homology,low abundance and low expression level in living cells,it is a hotspot to design novel strategies for miRNA detection with highly sensitive and selective.Based on this,we designed and constructed various multifunctional nanoprobes for cancer-related miRNAs detection in vitro/in vivo through different signal amplification methods.Distinguishing normal cells and different cancer cells is determined by fluorescence signal intensities,providing a reliable and effective method for early cancer diagnosis.Meanwhile,we fabricate a multi-functional nanocomposite as a theranostic nanoplatform for cancer diagnosis and treatment.Specifically,the works are presented as following:1.Highly sensitive and selective microRNA detection based on DNA-bio-bar-code and enzyme-assisted strand cycle exponential signal amplification:A highly sensitive and specific miRNA detection strategy is designed by using an exponential signal amplification system combining a DNA-bio-bar-code amplification with Nb BbvCI nicking enzyme-assisted strand cycle.This assay exhibits a linear range over 6 orders of magnitude with a low limit of detection.It also shows a good performance of analysis miRNA in cell lysates.2.Multiplex microRNAs imaging in living cell using DNA-capped-Au assembled hydrogels:We successfully incorporate DNA-capped Au nanoparticles and their complementary fluorescent dyes-modified DNA probes into a porous hydrogel network.in which hairpin-locked DNAzyme strands and active metal irons were loaded for simultaneously imaging multiplex miRNAs in living cells.The strand-displacement reaction and the DNAzyme-assisted target recycling dual-signal amplification enable to simultaneously assess the abundances of multiplex cancer-related miRNAs.The versatile and responsive DNA hydrogel system holds great potential for miRNA biomedical application,3.Imaging multiple microRNAs in living cell by ATP self-powered strand-displacement cascade amplification and chemo-photothermal for cancer therapy:Rational engineered Y-motif DNA structures are modified to CuS@mSiO2 loaded with numerous ATP(DOX).The strand displacement cascade amplification process is implemented by endogenous specific miRNA as trigger and ATP as fuel that mainly released from nanocarrier for simultaneously and sensitively imaging multiple cancer-related miRNAs in living cells.Meanwhile,CuS@mSiO2-Y/DOX nanocarriers displayed NIR-laser induced programmed chemotherapy and photothermal therapy for cancer.4.Fabricating aptamer-conjugated PEGylated-MoS2/Cu1.8S theranostic nanoplatform for multiplexed imaging diagnosis and chemo-photothermal cancer therapy:A multi-functional theranostic platform of AS1411 aptamer-conjugated PEGylated-MoS2/Cu1.8S nanoplatform combining disease diagnosis and multi-therapeutic is fabricated.The nanoplatform accomplishes photoacoustic imaging(PAI),photoluminescence imaging(PLI)and photothermal imaging(PTI)for in vitro and in vivo tumor cells imaging diagnosis.Meanwhile,the ATPMC nanoplatform can be used as a delivery of gene probe for intracellular miRNA detection aberrantly expressed in A459 cells and anticancer drug DOX for targeted chemo-photothermal therapy.