Mitochondrial polarity-triggered fluorogenic optical agent for exploring breast cancer

• A de novo concept using mitochondrial polarity as a new biomarker. • High sensitivity, photo-stability and desirable biocompatibility were performed. • Investigating of the pharmacokinetics of the optical agent. • In site imaging of mitochondrial polarity in breast cancer mice. • Evaluating the prospect of the probe in breast cancer diagnosis. Due to the lack of effective target analyte and real-time tools, noninvasive investigating breast cancer still remains a formidable challenge. Herein, we proposed, for the first time , mitochondrial polarity as a potential indicator, and further develop a new optical agent PNN for monitoring mitochondrial polarity variations to explore breast cancer. The solvatochromic quality of the probe PNN was intelligently designed based on canonical pull-push molecular structure tactics, and further effectively integrate targeting module for mitochondrial anchoring. Intriguingly, the fluorescence of probe PNN was specifically activated by polarity and exhibited high sensitivity, low biotoxicity and excellent biocompatibility performances. Capitalizing on these features, such a probe noninvasively achieved reporting abnormal polarity levels at the site of breast cancer with a high signal-to-background ratio, and the decreased mitochondrial polarity in mammary epithelial tissue cancer lesions was revealed. In addition, the pharmacokinetics of PNN was investigated, and the main liver metabolic pathways were confirmed. This study not only proposed mitochondrial polarity as a potential indicator for breast cancer but also provided a noninvasive imaging tool for intravital imaging of mitochondrial polarity, demonstrating its clinical promise for breast cancer disease.