A Tandem Cubic DNA Nanostructures Cell Membrane Surface Sensing Platform for In Situ Monitoring of Multiple Cytotoxicity-Related Biomarkers

Emerging organic pollutants (EOPs) are considered to exhibit extensive toxicity to the human body. However, monitoring of this toxicological process is hampered by the shortage of suitable methods to track endogenous biochemical factors at the living cell level. To solve this technical challenge, a cell surface fluorescent sensing platform using tandem cubic DNA nanostructures (tCDNs) as the main architecture is developed in this work. With the precise assembly of several prefabricated DNA wireframe modules, a set of linear nanosuperstructures can be efficiently hydrophobic anchored to the cell membrane surface. Furthermore, two different aptamer-based fluorescence recognition elements targeting adenosine triphosphate (ATP) and dopamine (DA) can be modified on top of tCDNs in an equidistant arrangement, serving as a core component for monitoring endogenous cellular biochemical factors. As a typical example, we used tetrabromobisphenol A bis(2-hydroxyethyl ether) (TBBPA-BHEE)-induced living cells as a toxic effect system to monitor the release of endogenous ATP and DA in a direct visualization manner. On this basis, the correlation between the concentrations of these two endogenous biochemical factors (ATP and DA) and different TBBPA-BHEE exposure conditions was explored. We believe that this work can provide a robust and promising tool for studying the cellular toxicological mechanisms caused by pollutants.