Resolving variable cell viability-induced false negative: Accurate and high-contrast fluorescence diagnosis of cancer enabled by dual organelle targeting and multiple microenvironmental parameters responsive versatile carbon dots

Abstract

Developing effective fluorescence-based diagnostic methods for cancer is of great importance but remains a major challenge owing to the low contrast and limited accuracy induced by the variable cell viability. To increase contrast and accuracy in cancer diagnosis, a dual-organelle-targeting and multiple-parameter-responsive design strategy is proposed here. As a proof of concept, versatile carbon dots (CDs) targeting mitochondria and nucleoli with ability to respond to three environmental parameters (mitochondrial membrane potential, viscosity, and RNA) are developed. These capabilities not only enable high-contrast and accurate imaging of cancer cells but also make the CDs highly robust against interference from environmental parameters alterations induced by cell damage or apoptosis. This new design strategy involving targeting of multiple organelles and multiple responsiveness to environmental parameters could inspire further research in bioactive material-based cancer imaging.