A HClO/miR-214 AND-Gated DNA Triangular Prism Nanoprobe for Stage-Resolved Imaging of Macrophage-to-Foam Cell Transformation in Atherosclerosis

Abstract Macrophage-to-foam cell transformation is a hallmark of early atherosclerosis. Accurate molecular imaging of this process remains analytically challenging due to insufficient cell-type selectivity and complex microenvironmental interference. To address these challenges, a dual-input AND-gated DNA triangular prism (TPCM) nanoprobe is developed. Fluorescence turn-on of this probe requires the simultaneous recognition of endogenous HClO and miR-214, which are concurrently elevated during foam-cell formation. Through spatial confinement, the rigid triangular prism scaffold accelerates DNAzyme catalytic kinetics by 2.52-fold compared to unconfined systems. In ox-LDL-stimulated RAW 264.7 macrophages, TPCM produces dose-dependent fluorescence responses that effectively distinguish distinct stages of foam-cell progression. These signal variations closely correlate with progressive lipid accumulation and the elevation of both HClO and miR-214, which are further corroborated by the expression of foam-cell markers MMP-9 and ITGβ1. The strict logic-gating mechanism significantly minimizes false-positive signals in non-target endothelial cells and LPS-induced inflammatory macrophage models. Beyond profiling foam-cell stages, TPCM successfully tracks the suppression of intracellular targets in response to pharmacological inhibitors (e.g., 4-aminobenzoic acid hydrazide and Calphostin C). This logic-gated platform can serve as a promising analytical tool for stage-resolved imaging of macrophage-to-foam cell transformation and evaluating related anti-atherosclerotic therapeutics.