An integrated electrochemical nanodevice for single-cell MiRNA-155 detection and drug evaluation

Abstract

Nanopipette-based platforms have emerged as a transformative tool for single-cell miRNA profiling and drug evaluation with the unique advantages of minimal invasiveness and high spatiotemporal resolution. Now the target detection and the drug delivery are separately operated with two steps, and the efflux of the cell results in a short intracellular retention of the drug molecules. In this paper, an integrated electrochemical nanodevice was fabricated for real-time monitoring of single-cell miRNA-155 and drug evaluation with one step, which was inserted into single cells by a three-dimensional micromanipulator. Upon exposure to miRNA-155, the stronger binding ability of the aptamer to miRNA-155 led to the detachment of Aptamer/HCOF/DOX from the nanopipette, changing the ionic current. Based on the ionic current, intracellular miRNA-155 level could be accurately quantified. The relative expression levels of miRNA-155 were calculated to be approximately 165.5 pM, 55.60 pM, 16.05 pM for single MDA-MB-231, MCF-7, and MCF-10A cells, respectively. Moreover, under the tumor acid microenvironment, the pH-sensitive HCOF structure facilitated controlled DOX release, allowing dynamic assessment of drug effects at the single-cell level, while minimizing off-target toxicity in normal cells due to microenvironment-specific drug activation. Due to the relative long retention time of the drug, the physiological changes of cells under different times of drug action could also be studied. This study highlights the potential of integrated electrochemical nanodevice for tracking and understanding the role of microRNA in screening new anticancer drug.