Strategies to promote permeation and vectorization, and reduce cytotoxicity of metal complex luminophores for bioimaging and intracellular sensing

Transition metal luminophores are emerging as important tools for intracellular imaging and sensing. Their putative suitability for such applications has long been recognised but poor membrane permeability and cytotoxicity were significant barriers that impeded early progress. In recent years, numerous effective routes to overcoming these issues have been reported, inspired in part, by advances and insights from the pharmaceutical and drug delivery domains. In particular, the conjugation of biomolecules but also other less natural synthetic species, from a repertoire of functional motifs have granted membrane permeability and cellular targeting. Such motifs can also reduce cytotoxicity of transition metal complexes and offer a valuable avenue to circumvent such problems leading to promising metal complex candidates for application in bioimaging, sensing and diagnostics. The advances in metal complex probes permeability/targeting are timely, as, in parallel, over the past two decades significant technological advances in luminescence imaging have occurred. In particular, super-resolution imaging is enormously powerful but makes substantial demands of its imaging contrast agents and metal complex luminophores frequently possess the photophysical characteristics to meet these demands. Here, we review some of the key vectors that have been conjugated to transition metal complex luminophores to promote their use in intra-cellular imaging applications. We evaluate some of the most effective strategies in terms of membrane permeability, intracellular targeting and what impact these approaches have on toxicity and phototoxicity which are important considerations in a luminescent contrast or sensing agent.