Mitochondria-targeting biocompatible fluorescent BODIPY probes.

An increase in the mitochondrial membrane potential (MMP) is a characteristic feature of cancer and cardiovascular disease. Therefore, it remains of crucial importance to develop new and improved fluorescent probes that are sensitive to the MMP, to report on mitochondrial health and function. Reported here are the design, synthesis, photophysical properties and biological characterisation of a series of BODIPY dyes, BODIPY-Mito-n, for mitochondria-targeted fluorescence imaging applications. Six BODIPY-Mito-n analogues were synthesised under mild conditions, and displayed excellent fluorescence quantum yields of between 0.59 and 0.72 in aqueous environments at physiological pH (pH = 7.4). The incorporation of poly(ethylene glycol) (PEG) chains to the triarylphosphonium cation moiety significantly improved the biocompatibility of the probes (BODIPY-Mito-6, IC50 > 50 µM). All BODIPY-Mito-n compounds demonstrated a high MMP-sensitive localisation in the mitochondria, with Pearson's correlation coefficients (PCC) of between 0.76 and 0.96. Compounds BODIPY-Mito-2 and BODIPY-Mito-6 revealed the highest sensitivity to the MMP, with a decrease in the emission intensity of 62% and 75%, respectively following MMP depolarisation. It is anticipated that the highest MMP sensitivity and enhanced biocompatibility of BODIPY-Mito-6 could lead to the development of new probes for mitochondrial imaging in the future.

Bioorthogonal dissociative rhenium(i) photosensitisers for controlled immunogenic cell death induction.

Photosensitisers for photoimmunotherapy with high spatiotemporal controllability are rare. In this work, we designed rhenium(i) polypyridine complexes modified with a tetrazine unit via a bioorthogonally activatable carbamate linker as bioorthogonally dissociative photosensitisers for the controlled induction of immunogenic cell death (ICD). The complexes displayed increased emission intensities and singlet oxygen (1O2) generation efficiencies upon reaction with trans-cyclooct-4-enol (TCO-OH) due to the separation of the quenching tetrazine unit from the rhenium(i) polypyridine core. One of the complexes containing a poly(ethylene glycol) (PEG) group exhibited negligible dark cytotoxicity but showed greatly enhanced (photo)cytotoxic activity towards TCO-OH-pretreated cells upon light irradiation. The reason is that TCO-OH allowed the synergistic release of the more cytotoxic rhenium(i) aminomethylpyridine complex and increased 1O2 generation. Importantly, the treatment induced a cascade of events, including lysosomal dysfunction, autophagy suppression and ICD. To the best of our knowledge, this is the very first example of using bioorthogonal dissociation reactions as a trigger to realise photoinduced ICD, opening up new avenues for the development of innovative photoimmunotherapeutic agents.

Photofunctional cyclometallated iridium(III) polypyridine methylsulfone complexes as sulfhydryl-specific reagents for bioconjugation, bioimaging and photocytotoxic applications.

We report herein near-infrared (NIR)-emitting cyclometallated iridium(III) complexes bearing a heteroaromatic methylsulfone moiety as sulfhydryl-specific reagents; one of the complexes was conjugated to cysteine and cysteine-containing peptides and proteins for bioimaging and photocytotoxic applications.

Luminescent rhenium(I) perfluorobiphenyl complexes as site-specific labels for peptides to afford photofunctional bioconjugates.

We report herein new luminescent rhenium(I) perfluorobiphenyl complexes that reacted specifically with the cysteine residue of the π-clamp sequence (FCPF) to afford novel peptide-based imaging reagents, photosensitisers for singlet oxygen and enzyme sensors.

Bioorthogonal control of the phosphorescence and singlet oxygen photosensitisation properties of iridium(III) tetrazine complexes.

In this work, we demonstrate bioorthogonal control of the phosphorescence and singlet oxygen photosensitisation properties of new iridium(iii) tetrazine complexes by different reaction partners; the system was exploited for organelle-specific staining and modulated photocytotoxic activity applications.

Modulation of emission and singlet oxygen photosensitisation in live cells utilising bioorthogonal phosphorogenic probes and protein tag technology.

Herein we report a strategy to utilise the bioorthogonal reactivity and phosphorogenic property of iridium(iii) polypyridine nitrone complexes and SNAP-tag protein for the modulation of emission and singlet oxygen (1O2) photosensitisation in live cells.

Luminescent Ruthenium(II) Polypyridine Complexes for a Wide Variety of Biomolecular and Cellular Applications.

Ruthenium(II) polypyridine complexes are one of the most extensively studied and developed systems in the family of luminescent transition-metal complexes. Notably, there has been a large amount of interest in the biological applications of these luminescent ruthenium(II) complexes because of their rich photophysical and photochemical properties. In this Viewpoint, we explore past and recent works on the possible biological and cellular applications of these promising complexes, with a focus on their use as bioimaging reagents, biomolecular probes, and phototherapeutic agents.