TY  - CONF
AU  - Čolović, Mirjana
AU  - Gajski, Goran
AU  - Domijan, Ana-Marija
AU  - Gerić, Marko
AU  - Savić, Nada
AU  - Parac-Vogt, Tatjana
AU  - Krstić, Danijela
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12229
AB  - Tungsten-based nanoparticles possess high density and capability to attenuate X-rays and thus have been studied as interesting candidates for the development of new-generation contrast-enhancing staining agents (CESAs) for computed tomography (CT). Polyoxotungstates, as polyoxoanions containing tungsten in its high oxidation state (W6+) were reported as promising CESA candidates to visualize long bones and kidney tissues. However, some polyoxotungstates induced side effects in toxicity studies in vivo, which could limit their clinical application. Thus, the aim of this study was to evaluate genotoxic effects in vitro of monolacunary Wells-Dawson polyoxotungstate, α2-K10P2W17O61.20H2O (lacunary WD) that was found as a potential contrast agent for CT in our previous studies in situ and in vitro. Lacunary WD was synthesized by following the reported procedure. The genotoxicity evaluation was performed by using the standard procedure for the alkaline comet assay. Briefly, human whole blood samples were taken from healthy male and female donors and exposed to different lacunary WD concentrations within the range of 10-6-10-4 mol/L, for 4 and 24 h at 37 °C. Then, 5 μL of whole blood was embedded into an agarose matrix and subsequently lysed (2.5 M NaCl, 100 mM EDTANa2, 10 mM Tris, 1% sodium sarcosinate, 1% Triton X-100, 10% DMSO, pH 10) overnight at 4 °C. After the lysis, the slides were placed into an alkaline solution (300 mM NaOH, 1 mM EDTANa2, pH 13) for 20 min at 4 °C to allow DNA unwinding and subsequently electrophoresed for 20 min at 1 V/cm. Finally, the slides were neutralized in 0.4 M Tris buffer (pH 7.5) for 5 min 3 times, stained with ethidium bromide (10 μg/mL), and analyzed at 250× magnification using an epifluorescence microscope (Zeiss, Göttingen, Germany) connected through a camera to an image analysis system (Comet Assay II; Perceptive Instruments Ltd., Haverhill, Suffolk, UK). One hundred randomly captured comets from each slide were examined. Multiple comparisons between groups were done by means of ANOVA on log-transformed data. Post hoc analyses of the differences were done by the Scheffé test. The percentage of tail DNA was determined to evaluate the level of DNA damage and genotoxicity potential. The obtained results showed that lacunary WD did not induce a statistically significant relative increase of tail DNA compared to the corresponding control at all investigated concentrations, after both 4 and 24 h exposure. Accordingly, the investigated promising contrast agent candidate could be regarded in further studies as toxicologically safe for healthy human blood cells from a genotoxicity point of view.
PB  - Niš : RAD Centre
C3  - RAD 2023 : 11th International Conference on Radiation Natural Sciences, Medicine, Engineering, Technology and Ecology : Book of Abstracts
T1  - In vitro genotoxicity assessment of a monolacunary Wells-Dawson nanocluster as a promising contrast agent candidate
SP  - 135
EP  - 135
DO  - 10.21175/rad.abstr.book.2023.23.3
ER  - 

@conference{
author = "Čolović, Mirjana and Gajski, Goran and Domijan, Ana-Marija and Gerić, Marko and Savić, Nada and Parac-Vogt, Tatjana and Krstić, Danijela",
year = "2023",
abstract = "Tungsten-based nanoparticles possess high density and capability to attenuate X-rays and thus have been studied as interesting candidates for the development of new-generation contrast-enhancing staining agents (CESAs) for computed tomography (CT). Polyoxotungstates, as polyoxoanions containing tungsten in its high oxidation state (W6+) were reported as promising CESA candidates to visualize long bones and kidney tissues. However, some polyoxotungstates induced side effects in toxicity studies in vivo, which could limit their clinical application. Thus, the aim of this study was to evaluate genotoxic effects in vitro of monolacunary Wells-Dawson polyoxotungstate, α2-K10P2W17O61.20H2O (lacunary WD) that was found as a potential contrast agent for CT in our previous studies in situ and in vitro. Lacunary WD was synthesized by following the reported procedure. The genotoxicity evaluation was performed by using the standard procedure for the alkaline comet assay. Briefly, human whole blood samples were taken from healthy male and female donors and exposed to different lacunary WD concentrations within the range of 10-6-10-4 mol/L, for 4 and 24 h at 37 °C. Then, 5 μL of whole blood was embedded into an agarose matrix and subsequently lysed (2.5 M NaCl, 100 mM EDTANa2, 10 mM Tris, 1% sodium sarcosinate, 1% Triton X-100, 10% DMSO, pH 10) overnight at 4 °C. After the lysis, the slides were placed into an alkaline solution (300 mM NaOH, 1 mM EDTANa2, pH 13) for 20 min at 4 °C to allow DNA unwinding and subsequently electrophoresed for 20 min at 1 V/cm. Finally, the slides were neutralized in 0.4 M Tris buffer (pH 7.5) for 5 min 3 times, stained with ethidium bromide (10 μg/mL), and analyzed at 250× magnification using an epifluorescence microscope (Zeiss, Göttingen, Germany) connected through a camera to an image analysis system (Comet Assay II; Perceptive Instruments Ltd., Haverhill, Suffolk, UK). One hundred randomly captured comets from each slide were examined. Multiple comparisons between groups were done by means of ANOVA on log-transformed data. Post hoc analyses of the differences were done by the Scheffé test. The percentage of tail DNA was determined to evaluate the level of DNA damage and genotoxicity potential. The obtained results showed that lacunary WD did not induce a statistically significant relative increase of tail DNA compared to the corresponding control at all investigated concentrations, after both 4 and 24 h exposure. Accordingly, the investigated promising contrast agent candidate could be regarded in further studies as toxicologically safe for healthy human blood cells from a genotoxicity point of view.",
publisher = "Niš : RAD Centre",
journal = "RAD 2023 : 11th International Conference on Radiation Natural Sciences, Medicine, Engineering, Technology and Ecology : Book of Abstracts",
title = "In vitro genotoxicity assessment of a monolacunary Wells-Dawson nanocluster as a promising contrast agent candidate",
pages = "135-135",
doi = "10.21175/rad.abstr.book.2023.23.3"
}

Čolović, M., Gajski, G., Domijan, A., Gerić, M., Savić, N., Parac-Vogt, T.,& Krstić, D.. (2023). In vitro genotoxicity assessment of a monolacunary Wells-Dawson nanocluster as a promising contrast agent candidate. in RAD 2023 : 11th International Conference on Radiation Natural Sciences, Medicine, Engineering, Technology and Ecology : Book of Abstracts
Niš : RAD Centre., 135-135.
https://doi.org/10.21175/rad.abstr.book.2023.23.3

Čolović M, Gajski G, Domijan A, Gerić M, Savić N, Parac-Vogt T, Krstić D. In vitro genotoxicity assessment of a monolacunary Wells-Dawson nanocluster as a promising contrast agent candidate. in RAD 2023 : 11th International Conference on Radiation Natural Sciences, Medicine, Engineering, Technology and Ecology : Book of Abstracts. 2023;:135-135.
doi:10.21175/rad.abstr.book.2023.23.3 .

Čolović, Mirjana, Gajski, Goran, Domijan, Ana-Marija, Gerić, Marko, Savić, Nada, Parac-Vogt, Tatjana, Krstić, Danijela, "In vitro genotoxicity assessment of a monolacunary Wells-Dawson nanocluster as a promising contrast agent candidate" in RAD 2023 : 11th International Conference on Radiation Natural Sciences, Medicine, Engineering, Technology and Ecology : Book of Abstracts (2023):135-135,
https://doi.org/10.21175/rad.abstr.book.2023.23.3 . .

TY  - JOUR
AU  - Isaković, Anđelka
AU  - Čolović, Mirjana B.
AU  - Ma, Tian
AU  - Ma, Xiang
AU  - Jeremić, Marija
AU  - Gerić, Marko
AU  - Gajski, Goran
AU  - Misirlić-Denčić, Sonja
AU  - Kortz, Ulrich
AU  - Krstić, Danijela Z.
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9952
AB  - Polyoxo-noble-metalates (PONMs), a class of molecular noble metal-oxo nanoclusters that combine features of both polyoxometalates and noble metals, are a promising platform for the development of next-generation antitumor metallodrugs. This study aimed to evaluate the antitumor potential against human neuroblastoma cells (SH-SY5Y), as well as toxicity towards healthy human peripheral blood cells (HPBCs), of five polyoxopalladates(II): (Na8[Pd13As8O34(OH)6]·42H2O (Pd13), Na4[SrPd12O6(OH)3(PhAsO3)6(OAc)3]·2NaOAc·32H2O (SrPd12), Na6[Pd13(AsPh)8O32]·23H2O (Pd13L), Na12[SnO8Pd12(PO4)8]·43H2O (SnPd12), and Na12[PbO8Pd12(PO4)8]·38H2O (PbPd12)), as the largest subset of PONMs. A pure inorganic, Pd13, was found as the most potent and selective antineuroblastoma agent with IC50 values (µM) of 7.2 ± 2.2 and 4.4 ± 1.2 for 24 and 48 h treatment, respectively, even lower than cisplatin (28.4 ± 7.4 and 11.6 ± 0.8). The obtained IC50 values (µM) for 24/48 h treatment with SrPd12 and Pd13L were 75.8 ± 6.7/76.7 ± 22.9 and 63.8 ± 3.6/21.4 ± 10.8, respectively, whereas SnPd12 and PbPd12 did not remarkably affect the SH-SY5Y viability (IC50 > > 100 µM). Pd13 caused depolarisation of inner mitochondrial membrane prior to superoxide ion hyperproduction, followed by caspase activation, DNA fragmentation and cell cycle arrest, all hallmarks of apoptotic cell death, and accompanied by an increase in acidic vesicles content, suggestive of autophagy induction. Importantly, Pd13 demonstrated the antitumor effect at concentrations not cytogenotoxic for normal HPBCs. On the contrary, SrPd12 and Pd13L at concentrations ≥ 1/3 IC50 (24 h) decreased HPBC viability and increased % tail DNA up to 42% and 3.05 times, respectively, related to control. SnPd12 and PbPd12, previously confirmed promising antileukemic agents, did not exhibit cytogenotoxicity to HPBCs, and thus could be regarded as tumor cell specific and selective drug candidates.
T2  - JBIC Journal of Biological Inorganic Chemistry
T1  - Selected polyoxopalladates as promising and selective antitumor drug candidates
VL  - 26
IS  - 8
SP  - 957
EP  - 971
DO  - 10.1007/s00775-021-01905-4
ER  - 

@article{
author = "Isaković, Anđelka and Čolović, Mirjana B. and Ma, Tian and Ma, Xiang and Jeremić, Marija and Gerić, Marko and Gajski, Goran and Misirlić-Denčić, Sonja and Kortz, Ulrich and Krstić, Danijela Z.",
year = "2021",
abstract = "Polyoxo-noble-metalates (PONMs), a class of molecular noble metal-oxo nanoclusters that combine features of both polyoxometalates and noble metals, are a promising platform for the development of next-generation antitumor metallodrugs. This study aimed to evaluate the antitumor potential against human neuroblastoma cells (SH-SY5Y), as well as toxicity towards healthy human peripheral blood cells (HPBCs), of five polyoxopalladates(II): (Na8[Pd13As8O34(OH)6]·42H2O (Pd13), Na4[SrPd12O6(OH)3(PhAsO3)6(OAc)3]·2NaOAc·32H2O (SrPd12), Na6[Pd13(AsPh)8O32]·23H2O (Pd13L), Na12[SnO8Pd12(PO4)8]·43H2O (SnPd12), and Na12[PbO8Pd12(PO4)8]·38H2O (PbPd12)), as the largest subset of PONMs. A pure inorganic, Pd13, was found as the most potent and selective antineuroblastoma agent with IC50 values (µM) of 7.2 ± 2.2 and 4.4 ± 1.2 for 24 and 48 h treatment, respectively, even lower than cisplatin (28.4 ± 7.4 and 11.6 ± 0.8). The obtained IC50 values (µM) for 24/48 h treatment with SrPd12 and Pd13L were 75.8 ± 6.7/76.7 ± 22.9 and 63.8 ± 3.6/21.4 ± 10.8, respectively, whereas SnPd12 and PbPd12 did not remarkably affect the SH-SY5Y viability (IC50 > > 100 µM). Pd13 caused depolarisation of inner mitochondrial membrane prior to superoxide ion hyperproduction, followed by caspase activation, DNA fragmentation and cell cycle arrest, all hallmarks of apoptotic cell death, and accompanied by an increase in acidic vesicles content, suggestive of autophagy induction. Importantly, Pd13 demonstrated the antitumor effect at concentrations not cytogenotoxic for normal HPBCs. On the contrary, SrPd12 and Pd13L at concentrations ≥ 1/3 IC50 (24 h) decreased HPBC viability and increased % tail DNA up to 42% and 3.05 times, respectively, related to control. SnPd12 and PbPd12, previously confirmed promising antileukemic agents, did not exhibit cytogenotoxicity to HPBCs, and thus could be regarded as tumor cell specific and selective drug candidates.",
journal = "JBIC Journal of Biological Inorganic Chemistry",
title = "Selected polyoxopalladates as promising and selective antitumor drug candidates",
volume = "26",
number = "8",
pages = "957-971",
doi = "10.1007/s00775-021-01905-4"
}

Isaković, A., Čolović, M. B., Ma, T., Ma, X., Jeremić, M., Gerić, M., Gajski, G., Misirlić-Denčić, S., Kortz, U.,& Krstić, D. Z.. (2021). Selected polyoxopalladates as promising and selective antitumor drug candidates. in JBIC Journal of Biological Inorganic Chemistry, 26(8), 957-971.
https://doi.org/10.1007/s00775-021-01905-4

Isaković A, Čolović MB, Ma T, Ma X, Jeremić M, Gerić M, Gajski G, Misirlić-Denčić S, Kortz U, Krstić DZ. Selected polyoxopalladates as promising and selective antitumor drug candidates. in JBIC Journal of Biological Inorganic Chemistry. 2021;26(8):957-971.
doi:10.1007/s00775-021-01905-4 .

Isaković, Anđelka, Čolović, Mirjana B., Ma, Tian, Ma, Xiang, Jeremić, Marija, Gerić, Marko, Gajski, Goran, Misirlić-Denčić, Sonja, Kortz, Ulrich, Krstić, Danijela Z., "Selected polyoxopalladates as promising and selective antitumor drug candidates" in JBIC Journal of Biological Inorganic Chemistry, 26, no. 8 (2021):957-971,
https://doi.org/10.1007/s00775-021-01905-4 . .