Rationally designed Ru(<scp>ii</scp>)-metallacycle chemo-phototheranostic that emits beyond 1000 nm

Abstract

Ruthenium complexes are emerging as potential complements to platinum drugs. They also show promise as photo-diagnostic and therapeutic agents. However, most ruthenium species studied to date as potential drugs are characterized by short excitation/emission wavelengths. This limits their applicability for deep-tissue fluorescence imaging and light-based therapeutic treatments. Here, we report a Ru(ii) metallacycle (Ru1100) that emits at ≥1000 nm. This system possesses excellent deep-tissue penetration capability (∼7 mm) and displays good chemo-phototherapeutic performance. <i>In vitro</i> studies revealed that Ru1100 benefits from good cellular uptake and produces a strong anticancer response against several cancer cell lines, including a cisplatin-resistant A549 cell line (IC₅₀ = 1.6 μM <i>vs.</i> 51.4 μM for cisplatin). On the basis of <i>in vitro</i> studies, it is concluded that Ru1100 exerts its anticancer action by regulating cell cycle progression and triggering cancer cell apoptosis. <i>In vivo</i> studies involving the use of a nanoparticle formulation served to confirm that Ru1100 allows for high-performance NIR-II fluorescence imaging-guided precise chemo-phototherapy in the case of A549 tumour mouse xenografts with no obvious side effects. This work thus provides a paradigm for the development of long-wavelength emissive supramolecular theranostic agents based on ruthenium.