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In situ Amplification of Intracellular MicroRNA with MNAzyme Nanodevices for Multiplexed Imaging, Logic Operation, and Controlled Drug Release.(acs nano)

       MicroRNAs (miRNAs) have participated in many biological processes, including cancer initiation, progression, and metastasis, indicative of potential diagnostic biomarkers and therapeutic targets. To tackle the low abundance of miRNAs in cells, MNAzymes (multicomponent nucleic acid enzymes) were used in constructing multifunctional nanodevices for stringent recognition and in situ signal amplification with gold nanorods as photothermal heater. The fluorescent turn-on nanodevices presented excellent specificity and sensitivity in visualizing trace amounts of miRNAs in single cell, allowing logic operation for graded cancer risk assessment and dynamic monitoring of therapy response. Meanwhile, through general molecular design, the aptamer-modified nanocarriers loaded with doxorubicin exclusively entered the target tumor cells, where drug release rates were spatial-temporally controlled by the modulation of endogenous miRNA expression. Integrated with miRNA profiling techniques, the designed nanodevices can provide general strategy for disease diagnosis, prognosis, and combination treatment with chemotherapy and gene therapy.