Cellular Uptake and Sensing Capability of Transition Metal Peptide Conjugates

There is a growing demand for luminophores customized for sensing and imaging in live cells and tissues. The demand has been driven by the evolution in diversity and sophistication of luminescence-based imaging technologies over the past 20. years. Conventionally, fluorophores used in cell imaging are conjugated organic molecules and although such species frequently have high fluorescence quantum yields they exhibit a range of limitations, including poor photostability, small Stokes shift, and short emission lifetimes (typically 1-10. ns), all of which can constrain their value in sensing applications. Luminescent transition metal probes, including in particular the polypyridyl coordination compounds of ruthenium and iridium, are valuable alternatives that can potentially address many of the limitations of organic fluorophores. However, until relatively recently, a significant barrier to the application of such probes has been the poor membrane permeability of transition metal complexes and perceptions that they are cytotoxic. Over the past decade a range of successful strategies have been applied to promoting uptake of transition metal luminophores based on their conjugation to biomolecules and biocompatible polymers. The application of signal peptides to drug delivery has yielded extensive insights into peptide targeting and this has inspired our group and others to exploit signal peptides to both permeate the cell membrane and to target metal complexes within living cells. Herein, we overview the applications of transition metal luminophore-peptide conjugates in live cell sensing and imaging. We describe the key types of peptide signaling sequences that have been exploited in this domain and the role they play in permeating the membrane and targeting within the cell. We examine representative examples of the application of peptide-conjugated metal complex probes in in-cell sensing and discuss future applications and the limitations of current probes that might be addressed by the coming generations of metal probe-based cell imaging and sensing tools.