Chemists from Hong Kong Baptist University have developed a novel peptide-conjugated theranostic toolbox for targeting gastrin-releasing peptide receptor (GRPr) in living cancer and immune cells. This theranostic agent could offer potential advantages in terms of being able to simultaneously monitor and treat a disease, whilst eliminating the risk of drug-probe interactions. It is the first known peptide-tethered iridium(III) complex developed as a GRPr bioimaging probe and modulator of GRPr activity.
The incorporation of a GRPr antagonist, JMV594, to an emissive iridium(III) complex was demonstrated as a viable strategy to enhance solubility, improve selectivity and lower toxicity of transition metal-based theranostics. This strategy not only endows the probe with desirable photophysical characteristics of the iridium(III) complex precursor, such as a large Stokes shift, long emission lifetime, and high photostability, but also grants the theranostic with excellent biochemical properties of peptides including improved selectivity and biocompatibility. In particular, its long emission lifetime enabled its luminescence signal to be readily distinguished from the interfering fluorescence of organic dyes by using a time-resolved technique. This theranostic agent may serve as a versatile probe to unmask the multi-functional roles of GRPr in living systems, while simultaneously providing therapeutic action via its ability to modulate GRPr function as well. The results of this study were published in the leading chemistry journal Angewandte Chemie International Edition.