Transition metals such as zinc, copper and iron play vital roles in maintaining physiological functions and homeostasis of living systems. Molecular imaging, including two-photon imaging (TPI), bioluminescence imaging (BLI) and photoacoustic imaging (PAI), could act as non-invasive toolkits for capturing dynamic events in living cells, tissues and whole animals. Herein, we review the recent progress in the development of molecular probes for essential transition metals and their biological applications. We emphasize the contributions of metallostasis to health and disease, and discuss the future research directions about how to harness the great potential of metal sensors.

Technology advances in genomics, proteomics, and metabolomics largely expanded the pool of potential therapeutic targets. Compared with the in vitro setting, cell-based screening assays have been playing a key role in the processes of drug discovery and development. Besides the commonly used strategies based on colorimetric and cell viability, we reason that methods that capture the dynamic cellular events will facilitate optimal hit identification with high sensitivity and specificity. Herein, we propose a live-cell screening strategy using structured illumination microscopy (SIM) combined with an automated cell colocalization analysis software, Cellprofiler^TM, to screen and discover drugs for mitochondria and lysosomes interaction at a nanoscale resolution in living cells. This strategy quantitatively benchmarks the mitochondria-lysosome interactions such as mitochondria and lysosomes contact (MLC) and mitophagy. The automatic quantitative analysis also resolves fine changes of the mitochondria-lysosome interaction in response to genetic and pharmacological interventions. Super-resolution live-cell imaging on the basis of quantitative analysis opens up new avenues for drug screening and development by targeting dynamic organelle interactions at the nanoscale resolution, which could facilitate optimal hit identification and potentially shorten the cycle of drug discovery.