DNA Dendrimer-Based Directed 3D Walking Nanomachine for the Sensitive Detection and Intracellular Imaging of miRNA

Abstract

Taking advantage of the remarkable processivity and membrane penetrability, the gold nanoparticle (AuNP)-based three-dimensional (3D) DNA walking nanomachine has induced tremendous promise in molecular diagnostics and cancer therapy, whereas the executive ability of this nanomachine was eventually limited because of the disordered assembly between the walker and the track. Therefore, we developed a well-directed 3D DNA walking nanomachine by employing a DNA dendrimer as the track for intracellular imaging with high directionality and controllability. The nanomachine was constructed on a DNA dendrimer decorated with a substrate strand serving as the DNA track and a DNAzyme restrained by a locking strand as the walker. In this system, the distribution of the substrate strand and DNAzyme on the DNA dendrimer could be precisely regulated to achieve expected goals because of the specificity and predictability of the Watson–Crick base pairing, paving an explicit route for each walker to move along the track. Moreover, such a DNA dendrimer-based nanomachine owned prominent stability and anti-interference ability. By choosing microRNA-21 as a model analyte, the nanomachine was applied for the imaging of microRNA-21 in different cell lines and the monitoring of the dynamic microRNA-21 expression level in cancer cells. Therefore, we believe that this directed DNA walking nanomachine will have a variety of applications in molecular diagnostics and biological function modulation.

Efficient Three-Dimensional DNA Nanomachine Guided by a Robust Tetrahedral DNA Nanoarray Structure for the Rapid and Ultrasensitive Electrochemical Detection of Matrix Metalloproteinase 2

“…Recently, the DNA walker, a novel dynamic nanomachine, − has garnered wide attention in bioimaging − and sensing systems , due to its flexible function and ingenious design. At present, most of the reported DNA walkers, such as one-dimensional (1D) , and two-dimensional (2D) DNA walkers, , are faced with difficulties of the limited number and length of arms resulting in the derailment of the DNA walker, further restricting the whole reaction rate and sensing efficiency.…”

A DNA Finite-State Machine Based on the Programmable Allosteric Strategy of DNAzyme

“…It provides a powerful tool for recording and processing time-related information and has attracted a wide range of attention from researchers. Owing to its high stability, modifiability, and programmability, DNA has promising applications in biosensing [ 8 , 9 , 10 ], disease diagnosis [ 11 , 12 , 13 ], molecular computing [ 14 , 15 , 16 , 17 ], information storage [ 18 , 19 , 20 ], nanomachines [ 21 , 22 ], and quantum computing [ 23 , 24 ]. It is one of the ideal materials for constructing artificial state machines.…”

Modular Engineering of a DNA Tetrahedron-Based Nanomachine for Ultrasensitive Detection of Intracellular Bioactive Small Molecules

“…15−18 Wang et al proposed a well-directed threedimensional walking nanomachine based on a DNA dendrimer track for the intracellular detection and imaging of microRNA (miRNA). 19 Miao et al presented a DNA bipedal walking nanomachine for nucleic acid detection, including miRNA, circulating tumor DNA, and viral DNA/RNA. 20 These studies demonstrated the effectiveness of DNA nanomachines in nucleic acid-based detection/diagnosis following the complementary base pairing principle.…”

“…Benefiting from the specificity and thermodynamics of Watson–Crick base pairing rules, artificial DNA nanomachines combine the advantages of programmability, self-assembly, and predictability, and they have been applied in the smart detection/diagnosis of diseases or controllable drug release. − Wang et al proposed a well-directed three-dimensional walking nanomachine based on a DNA dendrimer track for the intracellular detection and imaging of microRNA (miRNA) . Miao et al.…”