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) Ir III 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.

Green Light-Triggered Photocatalytic Anticancer Activity of Terpyridine-Based Ru(II) Photocatalysts

“…Besides that, IC 50 values of Ru1 – Ru3 are much better than those of the clinically used photosensitizer 5-ALA (151.1 μM) and cisplatin (25.3 μM) upon green light irradiation (29.56 J cm –2 ). The choice of light in PACT plays a vital role in achieving anticancer activity …”

“…Therefore, in photoactivated cancer therapy, controlled ROS generation has been used to selectively destroy cancer cells while sparing healthy ones . ROS are reported to damage cancer cells by primarily damaging their DNA, proteins, and cell membranes, ultimately triggering apoptosis or necrosis. − In photocatalytic cancer therapy, the photoresponsive metal complexes are reported to produce H 2 O 2 , OH • , and O 2 •– (as the byproducts of NADH oxidation) in addition to 1 O 2 (via a type II energy transfer pathway). − The encouraging photophysical properties, DFT calculation data, and enhanced light-triggered cytotoxicity indicated that Ru1 – Ru3 could have a notable ROS generation tendency. To examine the 1 O 2 production efficiency of Ru1 – Ru3 , 9,10-diphenyl anthracene (DPA) has been used.…”

“…12−15 The in-cell catalytic reactions (such as NADH/NAD(P)H oxidation) and ROS generation are ultimately reported to perturb energy metabolism and redox state in cancer cells selectively. 10,16 These further disrupt cell signaling cascades and/or modify gene expression regulation, ultimately causing tumor cell damage. 17−19 This novel concept, photocatalytic cancer therapy, has shown promising results in overcoming cisplatin resistance with high tumor selectivity both in vivo and in vitro.…”

“…This indicates that molecular O 2 is involved in the catalytic process, like the Ir(III) photocatalysts reported in the literature. [10][11][12]21 O 2 is probably involved in the regeneration of the Ru(II) active catalyst. 13−15 Cellular Uptake.…”

“…55 The absorption of green light might be useful for achieving green light-activated cancer therapy via incell NADH oxidation. 10,13 In DMSO solution, Ru3 showed an emission band near ca. 500 nm upon 425 nm excitation due to the presence of the anthracene moiety (Figure 2b).…”