Mild Acidosis‐Directed Signal Amplification in Tumor Microenvironment via Spatioselective Recruitment of DNA Amplifiers

Abstract

AbstractDNA biotechnology offers intriguing opportunities for amplification‐based sensitive detection. However, spatiotemporally‐controlled manipulation of signal amplification for in situ imaging of the tumor microenvironment remains an outstanding challenge. Here, we demonstrate a DNA‐based strategy that can spatial‐selectively amplify the acidic signal in the extracellular milieu of the tumor to achieve specific imaging with improved sensitivity. The strategy, termed mild acidosis‐targeted amplification (MAT‐amp), leverages the specific acidic microenvironment to engineer tumor cells with artificial DNA receptors through a pH (low) insertion peptide, which permits controlled recruitment of fluorescent amplifiers via a hybridization chain reaction. The acidosis‐responsive amplification cascade enables significant fluorescence enhancement in tumors with a reduced background signal in normal tissues, leading to improved signal‐to‐background ratio. These results highlight the utility of MAT‐amp for in situ imaging of the microenvironment characterized by pH disequilibrium.