Mitochondria-targeting cyclometalated iridium(III)-PEG complexes with tunable photodynamic activity

Steve Po Yam Li, Chris Tsan Shing Lau, Man Wai Louie, Yun Wah Lam, Shuk Han Cheng, Kenneth Kam Wing Lo

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204 Citations (Scopus)

Abstract

We present a new class of phosphorescent cyclometalated iridium(III) polypyridine poly(ethylene glycol) (PEG) complexes [Ir(N^C)2(bpy-CONH-PEG)](PF6) (bpy-CONH-PEG=4-(N-(2-(ω-methoxypoly-(1-oxapropyl))ethyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine, number average molecular weight (Mn)=5272.23, weight average molecular weight (Mw)=5317.38, polydispersity index (PDI)=1.009; HN^C=2-phenylpyridine, Hppy (1a), 2-((1,1'-biphenyl)-4-yl)pyridine, Hpppy (2a), 2-phenylquinoline, Hpq (3a), 2-phenylbenzothiazole, Hbt (4a), 2-(1-naphthyl)benzothiazole, Hbsn (5a)). The photophysical, photochemical, and biological properties of these complexes have been compared with those of their PEG-free counterparts [Ir(N^C)2(bpy-CONH-Et)](PF6) (bpy-CONH-Et=4-(N-ethylaminocarbonyl)-4'-methyl-2,2'-bipyridine; HN^C=Hppy (1b), Hpppy (2b), Hpq (3b), Hbt (4b), Hbsn (5b)). Upon irradiation, all the complexes exhibited intense and long-lived green to orange-red emission under ambient conditions. The emission was phosphorescence in nature and can be quenched by O2 with the generationofsinglet oxygen (1O2). The quantum yields for 1O2 production of the complexes in aerated DMSO (0.24-0.83) were found to be dependent on the excited-state lifetimes of the complexes, which can be altered using different cyclometalating ligands (N^C). Cell-based assays indicated that the PEG complexes were noncytotoxic in the dark (IC50>300μM); however, most of them became significantly cytotoxic upon irradiation (IC50=3.4-23.2μM). Laser-scanning confocal microscopy images revealed localization of complex 3a in the mitochondrial region of HeLa cells and the induction of rapid necrotic cell death upon light activation. Additionally, the lack of dark toxicity and potential application of the PEG complexes as a visualizing reagent have been demonstrated using zebrafish (Danio rerio) as an animal model.

Original languageEnglish
Pages (from-to)7519-7532
Number of pages14
JournalBiomaterials
Volume34
Issue number30
Early online date9 Jul 2013
DOIs
Publication statusPublished - 1 Oct 2013
Externally publishedYes

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