A mitochondria-targeting and polarity-sensitive fluorescent probe for cancer diagnosis

Abstract Polarity is a significant microenvironment-related parameter in living systems. It has been reported that the mitochondrial polarity level in cancer cells is remarkably lower than that in normal cells, demonstrating the potential of being a potential marker for the accurate diagnosis of cancers. Hence, in this work, a mitochondria-targeting fluorescent probe (NCT) with polarity-sensitive property was developed for cancer diagnosis based on the distinct mitochondrial polarity difference between cancerous cells and normal cells. For the design of the probe, we rationally combined two common ICT-based fluorophores (naphthalimide and coumarin) via a piperazine linker to endow the probe with more robust polarity-sensitive properties. The spectra results showed that all the fluorescence emission properties (emission intensity, quantum yield and lifetime) of probe were changed with the surrounding polarity, confirming the excellent polarity-sensitive merits of probe in solution. Subsequently, we explored the potential of this polarity-sensitive probe for the diagnosis of cancer. The imaging results demonstrated that NCT could emit strong fluorescence in the cancer cells, tissues and solid tumors (low-polarity environment), while almost no fluorescence was observed in normal cells, tissues and organs (high-polarity environment). In other words, NCT could differentiate cancer cells from normal cells in living systems based on the mitochondrial polarity difference of them. Consequently, we believe that this polarity-sensitive fluorescent probe could not only provide insight into the relationship between mitochondrial polarity and cancer, but also emerged as a potential tool for the diagnosis of tumors.