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Azo-Based Iridium(III) Complexes as Multicolor Phosphorescent Probes to Detect Hypoxia in 3D Multicellular Tumor Spheroids.

Sun L, Li G, Chen X, Chen Y, Jin C, Ji L, Chao H - Sci Rep (2015)

Bottom Line: Hypoxia is an important characteristic of malignant solid tumors and is considered as a possible causative factor for serious resistance to chemo- and radiotherapy.All of the iridium(III) complexes incorporate an azo group as an azo-reductase reactive moiety to detect hypoxia.Reduction of non-phosphorescent probes Ir1-Ir8 by reductases under hypoxic conditions resulted in the generation of highly phosphorescent corresponding amines for detection of hypoxic regions.

View Article: PubMed Central - PubMed

Affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, 510275, China.

ABSTRACT
Hypoxia is an important characteristic of malignant solid tumors and is considered as a possible causative factor for serious resistance to chemo- and radiotherapy. The exploration of novel fluorescent probes capable of detecting hypoxia in solid tumors will aid tumor diagnosis and treatment. In this study, we reported the design and synthesis of a series of "off-on" phosphorescence probes for hypoxia detection in adherent and three-dimensional multicellular spheroid models. All of the iridium(III) complexes incorporate an azo group as an azo-reductase reactive moiety to detect hypoxia. Reduction of non-phosphorescent probes Ir1-Ir8 by reductases under hypoxic conditions resulted in the generation of highly phosphorescent corresponding amines for detection of hypoxic regions. Moreover, these probes can penetrate into 3D multicellular spheroids over 100 μm and image the hypoxic regions. Most importantly, these probes display a high selectivity for the detection of hypoxia in 2D cells and 3D multicellular spheroids.

No MeSH data available.


Related in: MedlinePlus

(a) Cell viability of adherent 2D HeLa cells incubated with different concentrations of probes for 12 h under normoxic (I) and hypoxic (II) environment. (b) Growth inhibition assay in 3D spheroids. Growth curves of spheroids after various treatments. (c) Representative images of spheroids treated with eight probes (2.5 μM). Spheroids cultured in DMEM as a control; Scale bars = 50 μm.
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f8: (a) Cell viability of adherent 2D HeLa cells incubated with different concentrations of probes for 12 h under normoxic (I) and hypoxic (II) environment. (b) Growth inhibition assay in 3D spheroids. Growth curves of spheroids after various treatments. (c) Representative images of spheroids treated with eight probes (2.5 μM). Spheroids cultured in DMEM as a control; Scale bars = 50 μm.

Mentions: An ideal cellular probe for practical applications should minimally perturb living systems at the concentrations used. To verify the potential toxicity of Ir1-Ir8 to cells, MTT assays52 were conducted under normoxic and hypoxic conditions (Fig. 8a). The complexes were exposed to HeLa cells with different concentrations (2.5 μM, 5 μM, and 10 μM) for 12 h, and then the cell viability was evaluated by an MTT assay. The results for the normoxic and hypoxic conditions were similar for all of the compounds tested. Generally, at probe concentrations of 2.5 μM, HeLa cells exhibited viability higher than 80% after incubation for 12 h. These results suggested that under our experimental conditions (2.5 μM for 0.5 h incubation), these probes exhibited only a slight cytotoxic effect against HeLa cells.


Azo-Based Iridium(III) Complexes as Multicolor Phosphorescent Probes to Detect Hypoxia in 3D Multicellular Tumor Spheroids.

Sun L, Li G, Chen X, Chen Y, Jin C, Ji L, Chao H - Sci Rep (2015)

(a) Cell viability of adherent 2D HeLa cells incubated with different concentrations of probes for 12 h under normoxic (I) and hypoxic (II) environment. (b) Growth inhibition assay in 3D spheroids. Growth curves of spheroids after various treatments. (c) Representative images of spheroids treated with eight probes (2.5 μM). Spheroids cultured in DMEM as a control; Scale bars = 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4589790&req=5

f8: (a) Cell viability of adherent 2D HeLa cells incubated with different concentrations of probes for 12 h under normoxic (I) and hypoxic (II) environment. (b) Growth inhibition assay in 3D spheroids. Growth curves of spheroids after various treatments. (c) Representative images of spheroids treated with eight probes (2.5 μM). Spheroids cultured in DMEM as a control; Scale bars = 50 μm.
Mentions: An ideal cellular probe for practical applications should minimally perturb living systems at the concentrations used. To verify the potential toxicity of Ir1-Ir8 to cells, MTT assays52 were conducted under normoxic and hypoxic conditions (Fig. 8a). The complexes were exposed to HeLa cells with different concentrations (2.5 μM, 5 μM, and 10 μM) for 12 h, and then the cell viability was evaluated by an MTT assay. The results for the normoxic and hypoxic conditions were similar for all of the compounds tested. Generally, at probe concentrations of 2.5 μM, HeLa cells exhibited viability higher than 80% after incubation for 12 h. These results suggested that under our experimental conditions (2.5 μM for 0.5 h incubation), these probes exhibited only a slight cytotoxic effect against HeLa cells.

Bottom Line: Hypoxia is an important characteristic of malignant solid tumors and is considered as a possible causative factor for serious resistance to chemo- and radiotherapy.All of the iridium(III) complexes incorporate an azo group as an azo-reductase reactive moiety to detect hypoxia.Reduction of non-phosphorescent probes Ir1-Ir8 by reductases under hypoxic conditions resulted in the generation of highly phosphorescent corresponding amines for detection of hypoxic regions.

View Article: PubMed Central - PubMed

Affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, 510275, China.

ABSTRACT
Hypoxia is an important characteristic of malignant solid tumors and is considered as a possible causative factor for serious resistance to chemo- and radiotherapy. The exploration of novel fluorescent probes capable of detecting hypoxia in solid tumors will aid tumor diagnosis and treatment. In this study, we reported the design and synthesis of a series of "off-on" phosphorescence probes for hypoxia detection in adherent and three-dimensional multicellular spheroid models. All of the iridium(III) complexes incorporate an azo group as an azo-reductase reactive moiety to detect hypoxia. Reduction of non-phosphorescent probes Ir1-Ir8 by reductases under hypoxic conditions resulted in the generation of highly phosphorescent corresponding amines for detection of hypoxic regions. Moreover, these probes can penetrate into 3D multicellular spheroids over 100 μm and image the hypoxic regions. Most importantly, these probes display a high selectivity for the detection of hypoxia in 2D cells and 3D multicellular spheroids.

No MeSH data available.


Related in: MedlinePlus