In‐vitro and In‐vivo Photocatalytic Cancer Therapy with Biocompatible Iridium(III) Photocatalysts

Abstract

Photocatalytic anticancer profile of a IrIII photocatalyst (Ir3) with strong light absorption, high turnover frequency, and excellent biocompatibility is reported. Ir3 showed selective photo‐cytotoxicity against cisplatin‐ and sorafenib‐resistant cell lines while remaining dormant to normal cell lines in the dark. Ir3 exhibited excellent photo‐catalytic oxidation of cellular co‐enzyme, the reduced nicotinamide adenine dinucleotide phosphate (NADPH), and amino acids via a single electron transfer mechanism. The photo‐induced intracellular redox imbalance and change in mitochondrial membrane potential resulted in necrosis and apoptosis of cancer cells. Importantly, Ir3 exhibited high biocompatibility and photo‐catalytic anticancer efficiency as evident from in vivo zebrafish and mouse cancer models. To the best of our knowledge, Ir3 is the first IrIII based photocatalyst with such a high biocompatibility and photocatalytic anticancer therapeutic effect.

Phosphorescent Ir(iii) complexes derived from purine nucleobases

“…In addition to their applications in OLEDs, Ir(C^N) 2 (acac) complexes show remarkable nonlinear optical properties (NLO), 50 whereas [Ir(C^N) 2 (bipyridine)] + phosphors have recently focussed the interest due to their application in cell imaging 37,51–53 and photodynamic therapy. 54–57…”

“…In addition to their applications in OLEDs, Ir(C^N) 2 (acac) complexes show remarkable nonlinear optical properties (NLO), 50 whereas [Ir(C^N) 2 (bipyridine)] + phosphors have recently focussed the interest due to their application in cell imaging 37,[51][52][53] and photodynamic therapy. [54][55][56][57] In this context, to make use of the structure and biocompatibility of purine nucleobases (and nucleobase derivatives) for the preparation of iridium complexes with defined photophysical properties, is appealing. In fact, the design of most cyclometalated Ir(III) complexes for luminescence tagging relies on the covalent attachment of the metal complex to biologically relevant molecules 36 (biotin, [58][59][60] steroids, 60,61 sugars 62,63 ), which are able to interact with the biological receptors.…”

Metal‐Based Catalytic Drug Development for Next‐Generation Cancer Therapy

“…But achieving in‐cell catalysis for NAD + reduction or NADH oxidation by metal complex/s is highly challenging considering the extremely complicated reaction environments in cells. However, in recent years, significant breakthroughs have been achieved in terms of the transfer hydrogenation catalysis in cancer cells by various metal [Ru II , Rh III , Ir III , Os II ] complexes [13a,b,e,18–36] …”

“…The above idea of catalytic cancer photo‐therapy was confined within the in‐vitro studies (experiments in cells). To extend the scope of catalytic cancer photo‐therapy, we recently reported a highly phosphorescent and photo‐stable cyclometalated Ir III complex ( 38 ) with coumarin‐functionalized ligand (Figure 11(a)) [36] . The 38 is highly soluble in water and has significantly higher triplet excited state lifetime.…”

“… (a) Confocal imaging of Zebrafish (GFP‐transfected) after 12 h incubation with various concentrations of 38 indicating the biocompatible nature of 38 [36] . (b) Pictures of CT26 (colon carcinoma) tumors, isolated from mice after 14 d of various treatments indicating the in‐vivo anticancer activity of the photocatalyst 38 [36] . The figures are reproduced from Ref.…”