Simultaneous Imaging of Dual microRNAs in Cancer Cells through Catalytic Hairpin Assembly on a DNA Tetrahedron.

Accurate detection and imaging of tumor-related microRNA (miRNA) in living cells hold great promise for early cancer diagnosis and prognosis. One of the challenges is to develop methods that enable the identification of multiple miRNAs simultaneously to further improve the detection accuracy. Herein, a simultaneous detection and imaging method of two miRNAs was established by using a programmable designed DNA tetrahedron nanostructure (DTN) probe that includes a nucleolin aptamer (AS1411), two miRNA capture strands, and two pairs of metastable catalytic hairpins at different vertexes. The DTN probe exhibited enhanced tumor cell recognition ability, excellent stability and biocompatibility, and fast miRNA recognition and reaction kinetics. It was found that the DTN probe could specifically enter tumor cells, in which the capture strand could hybridize with miRNAs and initiate the catalytic hairpin assembly (CHA) only when the overexpressed miR-21 and miR-155 existed simultaneously, resulting in a distinct fluorescence resonance energy transfer signal and demonstrating the feasibility of this method for tumor diagnosis.

Sensitive Logic Nanodevices with Strong Response for Weak Inputs.

Sensitive sensing is critical when developing new calculation systems with weak input signals (ISs). In this work, a "weak-inputs-strong-outputs" strategy was proposed to guide the construction of sensitive logic nanodevices by coupling an input-induced reversible DNA computing platform with a hybridization chain reaction-based signal amplifier. By rational design of the sequence of computing elements (CEs) so as to avoid cross-talking between ISs and signal amplifier, the newly formed logic nanodevices have good sensitivity to the weak ISs even at low concentrations of CEs, and are able to perform YES, OR, NAND, NOR, INHIBIT, INHIBIT-OR and number classifier operation, showing that the DNA calculation proceeds in dilute solution medium that greatly improves the calculation proficiency of logic nanodevices without the confinement of the lithography process in nanotechnology.

Nucleolin-Targeted DNA Nanotube for Precise Cancer Therapy through Förster Resonance Energy Transfer-Indicated Telomerase Responsiveness.

Precise drug delivery holds great promise in cancer treatment but still faces challenges in controllable drug release in tumor cells specifically. Herein, a nucleolin-targeted and telomerase-responsive DNA nanotube for drug release was developed. First, a DNA nanosheet with four capture strands on its surface was prepared, which could bind and load ricin A chain (RTA). The RTA-loaded nanosheet was further converted into a DNA nanotube with a high Förster resonance energy transfer (FRET) efficiency in the presence of a Cy3-modified DNA fastener by hybridizing with the Cy5-modified DNA and another DNA-containing telomerase primer sequence along the long sides. Moreover, the aptamer of nucleolin was assembled on the DNA nanotube by combining with the hybrid chain at the terminal. The aptamer-functionalized and RTA-loaded DNA nanotube displayed enhanced tumor permeability and precise drug release in response to the telomerase in tumor cells, following the change of the FRET signal and RTA-induced cell death. Moreover, the DNA nanotube was applied successfully in vivo, and there was an obvious inhibition of tumor growth on xenograft-bearing mice following systemic administration, indicating that the constructed DNA nanotube represents a promising platform for precise RTA delivery in target cancer therapy.