ncoder (DRIVE), that enables the high-resolution molecular subtyping of triple-negative breast cancer (TNBC). Specifically, DRIVE integrates a tetrahedral DNA scaffold that is functionalized with two pairs of recognition and output modules responsive to apurinic/apyrimidinic endonuclease 1 (APE1) activity and specific microRNA (miRNA) expression. In the presence of APE1 and miRNA-21 (which are widely recognized as breast cancer biomarkers), the orthogonal recognition initiates a catalytic hairpin assembly (CHA) reaction that links a single DRIVE into a linear DNA nanostructure, thus significantly amplifying a monochromatic FAM signal. In TNBC subtypes that are characterized by the coexpression of APE1, miRNA-21, and miRNA-210, the cross-CHA makes a single DRIVE-form network DNA nanostructure, achieving the dichromatic FAM/Cy5 signal output. It is demonstrated that an approximately 4-fold enhancement in reaction kinetics of DRIVE is observed in comparison with that of individually dispersed probes. The dual-signal output enables a statistically significant differentiation of TNBC cells from other breast cancer subtypes. Together, this advance facilitates precise TNBC subtyping and provides great potential for accurate cancer diagnostics and personalized therapeutic strategies.
Chen et al. (Sun,) studied this question.
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