An acidic pH-activatable fluorescent probe for MUC1 detection and the precise imaging of MCF-7 cells

Mucin 1 (MUC1), a pivotal cancer biomarker, is overexpressed on MCF-7 cells, which has stimulated the construction of numerous aptamer-based fluorescent probes for breast cancer diagnosis. However, MUC1 is also present in the serum of cancer patients and expressed at low levels on the surface of normal cells, which may result in false-positive signals upon recognition by aptamers. In this work, a gold nanoparticle (AuNPs)-based fluorescent probe termed b-NPs was proposed by utilizing the acidic tumor microenvironment and pH-responsive single-stranded DNA (f-DNA) with conformational switching capabilities. In neutral pH environments, f-DNA can maintain a freely extended conformation, thereby shielding MUC1-aptamer and restricting its binding to MUC1. When the pH drops to 6.5, partial cytosines in f-DNA become protonated, accompanied by the formation of a compact C-quadruplex and stabilized by protonated cytosine-cytosine base pairs, thereby exposing the MUC1-aptamer and promoting its specific binding to MUC1. Ultimately, benefiting from its high specificity and low cytotoxicity, b-NPs was successfully applied to MUC1 detection, and the limit of detection (LOD) was as low as 0.06 nM. Meanwhile, in comparison with the cellular imaging performance observed in MCF-10A and HepG2 cells, b-NPs displayed high imaging accuracy toward MCF-7 cells.