Single‐Cell Quantification of a Highly Biocompatible Dinuclear Iridium(III) Complex for Photocatalytic Cancer Therapy

Abstract

Quantifying the content of metal‐based anticancer drugs within single cancer cells remains a challenge. Here, we used single‐cell inductively coupled plasma mass spectrometry to study the uptake and retention of mononuclear (Ir1) and dinuclear (Ir2) IrIII photoredox catalysts. This method allowed rapid and precise quantification of the drug in individual cancer cells. Importantly, Ir2 showed a significant synergism but not an additive effect for NAD(P)H photocatalytic oxidation. The lysosome‐targeting Ir2 showed low dark toxicity in vitro and in vivo. Ir2 exhibited high photocatalytic therapeutic efficiency at 525 nm with an excellent photo‐index in vitro and in tumor‐bearing mice model. Interestingly, the photocatalytic anticancer profile of the dinuclear Ir2 was much better than the mononuclear Ir1, indicating for the first time that dinuclear metal‐based photocatalysts can be applied for photocatalytic anticancer treatment.

Current status of iridium-based complexes against lung cancer

“…Fan et al reported a novel photostable phosphorescent organometallic binuclear iridium (III) complex 44 (Figure 4), which is an excellent photosensitizer and efficient photocatalyst for NAD(P)H and amino acid oxidation with significantly higher photocytotoxicity at 525 nm than its mononuclear structure (Fan et al, 2022). In addition, compound 44 also possesses lysosome targeting and high biocompatibility, showing significantly high light-activated anticancer activity against A549 lung cancer cells and HepG2 tumor-bearing mouse models in vitro and in vivo (Table 1).…”

Tunable Emissive Ir(III) Benzimidazole‐quinoline Hybrids as Promising Theranostic Lead Compounds

“…The necessity of finding additional metallodrugs to cisplatin is boosting research into new, and very promising, metal‐based structures such as those derived from Ru(II), Au(I/III), very recently Ir(III) [1] or combination of those [2–4] . The key point is to deliver drugs able to reveal their therapeutic potential by a mechanism of action different from that of cisplatin, in order to avoid the so‐called ‘platinum resistance’ [5] and its adverse side effects [6] .…”

“…The necessity of finding additional metallodrugs to cisplatin is boosting research into new, and very promising, metal-based structures such as those derived from Ru(II), Au(I/III), very recently Ir(III) [1] or combination of those. [2][3][4] The key point is to deliver drugs able to reveal their therapeutic potential by a mechanism of action different from that of cisplatin, in order to avoid the so-called 'platinum resistance' [5] and its adverse side effects. [6] Cyclometallated Ir(III) complexes with the general formula [Ir(C ^N) 2 (N ^N)] + , present a variety of cellular targets, from mitochondria [7] or lysosomes to endoplasmic reticulum among others organelles, [8] thus triggering different cellular therapeutic response.…”

Axisymmetric bis-tridentate Ir(iii) photoredox catalysts for anticancer phototherapy under hypoxia

“…Previously, we reported terpyridyl-Ir( iii ) complexes of the type [Ir(N^N^N)(C^N)Cl] + as metal photocatalysts to induce NADH photocatalysis in cancer cells. 10 However, the chloride ligand may undergo hydrolysis, similar to cisplatin. Moreover, the existence of stereoisomers may also bring unanticipated side effects.…”

“…13 Thus, dimethylamine was introduced as the auxochrome to construct the symmetrical tridentate N^N^N ligand 4-([2,2′:6′,2′′-terpyridin]-4′-yl)- N , N -dimethylaniline ( Ir2 ) to enhance the light absorption property at a longer wavelength. 15 According to our previous work, 10 we assumed that cyclometallation can improve the photophysical properties of bis-tridentate Ir( iii ) photocatalyst. Thus the symmetrical C^N^C ligand 2,4,6-triphenylpyridine was also designed to construct the axisymmetric cyclometalated Ir( iii ) photocatalyst ( Ir3 ) for comparative study with Ir2 .…”