title: Target-Catalyzed DNA Four-Way Junctions for CRET Imaging of MicroRNA, Concatenated Logic Operations, and Self-Assembly of DNA Nanohydrogels for Targeted Drug Delivery.
abstract: Here we report a target-catalyzed DNA four-way junction (DNA-4WJ) on the basis of toehold-mediated DNA strand displacement reaction (TM-SDR), which is readily applied in enzyme-free amplified chemiluminescence resonance energy transfer (CRET) imaging of microRNA. In this system, the introduction of target microRNA-let-7a (miR-let-7a) activates a cascade of assembly steps with four DNA hairpins, followed by a disassembly step in which the target microRNA is displaced and released from DNA-4WJ to catalyze the self-assembly of additional branched junctions. As a result, G-quadruplex subunit sequences and fluorophore fluorescein amidite (FAM) are encoded in DNA-4WJ in a close proximity, stimulating a CRET process in the presence of hemin/K(+) to form horseradish peroxidase (HRP)-mimicking DNAzyme that catalyzes the generation of luminol/H2O2 chemiluminescence (CL), which further transfers to FAM. The background signal is easily reduced using magnetic graphene oxide (MGO) to remove unreacted species through magnetic separation, which makes a great contribution to improve the detection sensitivity and achieves a detection limit as low as 6.9 fM microRNA-let-7a (miR-let-7a). In addition, four-input concatenated logic circuits with an automatic reset function have been successfully constructed relying on the architecture of the proposed DNA-4WJ. More importantly, DNA nanohydrogels are self-assembled using DNA-4WJs as building units after centrifugation, which are driven by liquid crystallization and dense packaging of building units. Moreover, the DNA nanohydrogels are readily functionalized by incorporating with aptamers, bioimaging agents, and drug loading sites, which thus are served as efficient nanocarriers for targeted drug delivery and cancer therapy with high loading capacity and excellent biocompatibility.
authors.affiliation: Shandong Province Key Laboratory of Detection Technology for Tumor Markers, School of Chemistry and Chemical Engineering, Linyi University , Linyi 276005, China.|Collaborative Innovation Center for Marine Biomass Fiber Materials and Textiles, College of Chemical Science and Engineering, Laboratory of Fiber Materials and Modern Textiles, the Growing Base for State Key Laboratory, Shandong Sino-Japanese Center for Collaborative Research of Carbon Nanomaterials, Qingdao University , Qingdao 266071, China.
authors.forename: Sai
authors.initials: S
authors.lastname: Bi
authors.affiliation: Key Laboratory of Sensor Analysis of Tumor Marker, Ministry of Education, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology , Qingdao 266042, China.
authors.forename: Bao
authors.initials: B
authors.lastname: Xiu
authors.affiliation: Key Laboratory of Sensor Analysis of Tumor Marker, Ministry of Education, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology , Qingdao 266042, China.
authors.forename: Jiayan
authors.initials: J
authors.lastname: Ye
authors.affiliation: Key Laboratory of Sensor Analysis of Tumor Marker, Ministry of Education, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology , Qingdao 266042, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Dong
mesh_terms: D002138:Calibration; D016923:Cell Death; D045744:Cell Line, Tumor; D021881:DNA, Catalytic / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems; D031541:Fluorescence Resonance Energy Transfer; D006108:Graphite; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D008128:Logic; D049449:Luminescence; D060328:Magnetic Phenomena; D035683:MicroRNAs / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure
chemical_list: D021881:DNA, Catalytic; D035683:MicroRNAs; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006108:Graphite; D004317:Doxorubicin
keywords: DNA four-way junction; DNA nanohydrogels; concatenated logic circuits; targeted drug delivery; toehold-mediated strand displacement