A Mitochondria‐Targeted Photosensitizer Showing Improved Photodynamic Therapy Effects Under Hypoxia

Abstract

Organelle-targeted photosensitizers have been reported to be effective photodynamic therapy (PDT) agents. In this work, we designed and synthesized two iridium(III) complexes that specifically stain the mitochondria and lysosomes of living cells, respectively. Both complexes exhibited long-lived phosphorescence, which is sensitive to oxygen quenching. The photocytotoxicity of the complexes was evaluated under normoxic and hypoxic conditions. The results showed that HeLa cells treated with the mitochondria-targeted complex maintained a slower respiration rate, leading to a higher intracellular oxygen level under hypoxia. As a result, this complex exhibited an improved PDT effect compared to the lysosome-targeted complex, especially under hypoxia conditions, suggestive of a higher practicable potential of mitochondria-targeted PDT agents in cancer therapy.

Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy

“…262 In addition, lysosomal targeted PSs to directly activate cell apoptosis and nuclear targeted PSs to introduce in situ double strand breaks and alkali-labile lesions in the DNA molecules have been widely studied. Organelle-targeted PSs that specifically accumulate in hypersensitive subcellular locations, such as nucleus, 265, 266 lysosome, 267 and mitochondrion, 268, 269 have provided an elevated level of controllable photosensitization. These approaches on whether and to what extent subcellular localization of PSs may influence the overall efficiency of photodynamic therapy have been concisely studied and summarized.…”

Hybrid TiO2–Ruthenium Nano‐photosensitizer Synergistically Produces Reactive Oxygen Species in both Hypoxic and Normoxic Conditions

“…[9] One of such complexes is cis -bis(isothiocyanato)bis(2,2’-bipyridyl-4,4’-dicarboxylato)ruthenium(II), abbreviated N3. This complex, which absorbs light in the UV and visible wavelengths, possesses multiple triplet states that can be populated by both metal to ligand charge transfer ( 3 MLCT) and intra-ligand charge transfer ( 3 π−π*) mechanisms.…”

“…[13e] Similarly, toxicity studies with organometallic ruthenium complexes have also been conducted in tumor cells and mice, and show limited toxicity. [9b] …”

Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells

“…These lifetimes, especially that of 2,a re about 19 times longer than for aqueous solutions (in air), thus suggesting that the complexes reside in am ore hydrophobic and hypoxic environment in living cells,f actors known to enhance the phosphorescence lifetimes of photosensitizers. [12] 1 O 2 generation by 1 and 2 under l = 465 nm (blue) light irradiation was detected by electron paramagnetic resonance (EPR) spectroscopy using 2,2,6,6-tetramethylpiperidine (TEMP) as as pin-trap.T he characteristic triplet-of-triplets for the 2,2,6,6-tetramethylpiperidine-1-oxyl radical was observed under irradiation. An Table S7).…”