Cascade Circuits on Self-Assembled DNA Polymers for Targeted RNA Imaging In Vivo

Abstract

DNA molecular probes have emerged as a powerful tool for RNA imaging. Hurdles in cell-specific delivery and other issues such as insufficient stability, limited sensitivity, or slow reaction kinetics, however, hinder the further application of DNA molecular probes in vivo. Herein, we report an aptamer-tethered DNA polymer for cell-specific transportation and amplified imaging of RNA in vivo via a DNA cascade reaction. DNA polymers are constructed through an initiator-triggered hybridization chain reaction using two functional DNA monomers. The prepared DNA polymers show low cytotoxicity and good stability against nuclease degradation and enable cell-specific transportation of DNA circuits via aptamer−receptor binding. Moreover, assembling the reactants of hairpins C1 and C2 on the DNA polymers accelerates the response kinetics and improves the sensitivity of the cascade reaction. We also show that the DNA polymers enable efficient imaging of microRNA-21 in live cells and in vivo via intravenous injection. The DNA polymers provide a valuable platform for targeted and amplified RNA imaging in vivo, which holds great implications for early clinical diagnosis and therapy.

Multivalent self-assembled nano string lights for tumor-targeted delivery and accelerated biomarker imaging in living cells and in vivo

“…It has been reported that the aptamer AS1411 could specifically bind to nucleolin which was overexpressed on cancer cells. 36–38 As shown in Fig. 5a, compared with the nanoprobe incubated with HEK-293 cells, an obviously enhanced fluorescence intensity was observed for HeLa cells, revealing the targeted capability of AS1411.…”

“…In this design, AS1411 aptamers on the DNA nanowires can specifically recognize the nucleolin receptors that are overexpressed in cancer cells and then internalize them into the tumor cells for target recognition. 36–38 In cancer cells, the targeted miRNAs can initiate the strand displacement reaction (SDR) along the DNA nanowire to recover fluorescence signals. On account of the spatial confinement effect in a confined room of the DNA nanowire, the reaction rate and efficiency of the target-stimulated SDR were obviously increased compared to those of the traditional SDR.…”

Fuel‐Powered DNA Nanomachines for Biosensing and Cancer Therapy

“…Reproduced from Ref. [53] with permission from American Chemical Society. compact space, accelerating the response kinetics with 3.5 times faster than the traditional CHA.…”

A Cell-Anchored and Self-Calibrated DNA Nanoplatform for in Situ Imaging and Quantification of Endogenous MicroRNA in Live Cells: Introducing Two Controls to Normalize the Sensing Signals

“…[14][15][16][17] While these methods have reached the goal of delivering cargo into specific cells, there is still a need to improve the performance of the delivery system, so as to reduce costs, simplify the preparation process, improve the biocompatibility, and generalize the system to multiple cells. Given these findings, DNA self-assembly based on the hybridization chain reaction (HCR) [18][19][20] is a good choice, which can be easily synthesized by roughly mixing DNA strands. Moreover, to achieve generalized detection, the DNA nanosystem is also require to be able to recognize Page 2 of 30 CCS Chemistry multiple cells, whether the tumor or normal cells.…”