Predarska, Ivana

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  • Predarska, Ivana (6)
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Author's Bibliography

The effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo

Komazec, Teodora; Mihajlović, Ekatarina; Bovan, Dijana; Mijatović, Sanja; Predarska, Ivana; Hey-Hawkins, Evamarie; Kaluđerović, Goran N.; Maksimović-Ivanić, Danijela

(Belgrade, Serbia: Serbian Associaton for Cancer Research, 2023)

TY  - CONF
AU  - Komazec, Teodora
AU  - Mihajlović, Ekatarina
AU  - Bovan, Dijana
AU  - Mijatović, Sanja
AU  - Predarska, Ivana
AU  - Hey-Hawkins, Evamarie
AU  - Kaluđerović, Goran N.
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - https://www.sdir.ac.rs/oncology-insights/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6215
AB  - Background: Active contribution of cyclooxygenase enzymes (COX) and their products, in particular prostaglandin E2, to tumor progression makes this enzyme an attractive target for molecular therapy in cancer. The combination of conventional chemotherapeutic drugs with COX1/2 inhibitors, and further enhancement of their delivery into target tissue can be a highly prospective approach in cancer therapy, especially in advanced stages. Accordingly, a cytostatic and anti-inflammatory drug conjugate was synthesised, as well as its immobilization in mesoporous nanostructured silica SBA-15. Detailed evaluation of the cytotoxic potential and the mechanism of action of this conjugate and the appropriate material on B16 cells was further performed in vitro and in vivo. Material and Methods: Cell viability of B16 melanoma cells was determined by MTT and CV assays. Cell morphology was estimated by hematoxylin–eosin and Oil Red O staining using light microscopy, while changes in the nuclei were validated by PI staining using fluorescent microscopy. Differentiation of melanoma cells was determined by measurement of tyrosinase activity and the presence of melanin. Syngeneic C57BL/6 mice model was used for in vivo assessment of the tumorigenic potential of B16 cells exposed to free and SBA-15 loaded conjugate in vitro, as well as for the evaluation of the antitumor potential of the experimental substances given in the therapeutic regimen. Results and Conclusion: Exposure to free or immobilized cisplatin-ibuprofen conjugate decreased the viability of the B16 cell culture while morphology of survived cells was changed. Cytoplasm of enlarged and elongated cells showed intensive granularity with enhanced lipid content and huge irregularly shaped nuclei with prominent heterochromatin foci, all of which indicated senescent state. Increased activity of tyrosinase and the presence of melanin compared to the control, referred to the differentiation of melanoma cells toward primary phenotype. Further inoculation of pretreated B16 cells into C57BL/6 mice showed decreased potential to form tumor in comparison to tumorigenic potential of untreated cells. Additionally, in vivo application of free and SBA-15 immobilized conjugate in therapeutic regiment led to statistically significant reduction of tumor volume, with only fewer signs of toxicity compared to cisplatin as positive control. New knowledge about this compound and corresponding material is reflected in their antitumor potential on mouse melanoma cells, which opens numerous possibilities for further research.
PB  - Belgrade, Serbia: Serbian Associaton for Cancer Research
C3  - Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
T1  - The effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo
SP  - 62
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6215
ER  - 
@conference{
author = "Komazec, Teodora and Mihajlović, Ekatarina and Bovan, Dijana and Mijatović, Sanja and Predarska, Ivana and Hey-Hawkins, Evamarie and Kaluđerović, Goran N. and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Background: Active contribution of cyclooxygenase enzymes (COX) and their products, in particular prostaglandin E2, to tumor progression makes this enzyme an attractive target for molecular therapy in cancer. The combination of conventional chemotherapeutic drugs with COX1/2 inhibitors, and further enhancement of their delivery into target tissue can be a highly prospective approach in cancer therapy, especially in advanced stages. Accordingly, a cytostatic and anti-inflammatory drug conjugate was synthesised, as well as its immobilization in mesoporous nanostructured silica SBA-15. Detailed evaluation of the cytotoxic potential and the mechanism of action of this conjugate and the appropriate material on B16 cells was further performed in vitro and in vivo. Material and Methods: Cell viability of B16 melanoma cells was determined by MTT and CV assays. Cell morphology was estimated by hematoxylin–eosin and Oil Red O staining using light microscopy, while changes in the nuclei were validated by PI staining using fluorescent microscopy. Differentiation of melanoma cells was determined by measurement of tyrosinase activity and the presence of melanin. Syngeneic C57BL/6 mice model was used for in vivo assessment of the tumorigenic potential of B16 cells exposed to free and SBA-15 loaded conjugate in vitro, as well as for the evaluation of the antitumor potential of the experimental substances given in the therapeutic regimen. Results and Conclusion: Exposure to free or immobilized cisplatin-ibuprofen conjugate decreased the viability of the B16 cell culture while morphology of survived cells was changed. Cytoplasm of enlarged and elongated cells showed intensive granularity with enhanced lipid content and huge irregularly shaped nuclei with prominent heterochromatin foci, all of which indicated senescent state. Increased activity of tyrosinase and the presence of melanin compared to the control, referred to the differentiation of melanoma cells toward primary phenotype. Further inoculation of pretreated B16 cells into C57BL/6 mice showed decreased potential to form tumor in comparison to tumorigenic potential of untreated cells. Additionally, in vivo application of free and SBA-15 immobilized conjugate in therapeutic regiment led to statistically significant reduction of tumor volume, with only fewer signs of toxicity compared to cisplatin as positive control. New knowledge about this compound and corresponding material is reflected in their antitumor potential on mouse melanoma cells, which opens numerous possibilities for further research.",
publisher = "Belgrade, Serbia: Serbian Associaton for Cancer Research",
journal = "Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia",
title = "The effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo",
pages = "62",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6215"
}
Komazec, T., Mihajlović, E., Bovan, D., Mijatović, S., Predarska, I., Hey-Hawkins, E., Kaluđerović, G. N.,& Maksimović-Ivanić, D.. (2023). The effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
Belgrade, Serbia: Serbian Associaton for Cancer Research., 62.
https://hdl.handle.net/21.15107/rcub_ibiss_6215
Komazec T, Mihajlović E, Bovan D, Mijatović S, Predarska I, Hey-Hawkins E, Kaluđerović GN, Maksimović-Ivanić D. The effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia. 2023;:62.
https://hdl.handle.net/21.15107/rcub_ibiss_6215 .
Komazec, Teodora, Mihajlović, Ekatarina, Bovan, Dijana, Mijatović, Sanja, Predarska, Ivana, Hey-Hawkins, Evamarie, Kaluđerović, Goran N., Maksimović-Ivanić, Danijela, "The effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo" in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia (2023):62,
https://hdl.handle.net/21.15107/rcub_ibiss_6215 .

Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model

Komazec, Teodora; Mihajlović, Ekatarina; Bovan, Dijana; Mijatović, Sanja; Predarska, Ivana; Kaluđerović, Goran N.; Hey-Hawkins, Evamarie; Maksimović-Ivanić, Danijela

(Belgrade: Faculty of Chemistry, 2023)

TY  - CONF
AU  - Komazec, Teodora
AU  - Mihajlović, Ekatarina
AU  - Bovan, Dijana
AU  - Mijatović, Sanja
AU  - Predarska, Ivana
AU  - Kaluđerović, Goran N.
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6217
AB  - Overexpression of cyclooxygenase (COX) and thus, prostaglandin E2 in numerous cancers
justified COX inhibitors testing in cancer prevention or treatment 1. Conjugate molecules of
COX inhibitors and common chemotherapeutic drugs, as well as their immobilization in
nanoparticles that increases drug delivery and accumulation in tumor tissue, can potentially
improve approaches in cancer therapy. Cisplatin-naproxen conjugate and corresponding
SBA-15 counterpart decreased the viability of B16 cells. Enlarged and elongated cells with
distinctly granular cytoplasm and the increased presence of lipid droplets were noticed
after haematoxylin–eosin and Oil Red O staining of treated cultures. In addition, enormous
nuclei and markedly heterochromatin foci were confirmed by PI staining indicating
establishment of senescent state upon the treatment. Alongside, differentiation of
melanoma cells toward melanocytes was demonstrated by elevated tyrosinase activity and
presence of melanin, thus leading to reduced tumorigenic potential in vivo. In addition,
cisplatin-naproxen conjugate and corresponding SBA-15 counterpart significantly reduced
melanoma growth in C57BL/6 mice, with lesser signs of toxicity compared to cisplatin as
a positive control. Strong antitumor potential of both, free and immobilized conjugates on
mouse melanoma cells opens numerous possibilities for further research.
PB  - Belgrade: Faculty of Chemistry
C3  - Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
T1  - Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model
SP  - 97
EP  - 98
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6217
ER  - 
@conference{
author = "Komazec, Teodora and Mihajlović, Ekatarina and Bovan, Dijana and Mijatović, Sanja and Predarska, Ivana and Kaluđerović, Goran N. and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Overexpression of cyclooxygenase (COX) and thus, prostaglandin E2 in numerous cancers
justified COX inhibitors testing in cancer prevention or treatment 1. Conjugate molecules of
COX inhibitors and common chemotherapeutic drugs, as well as their immobilization in
nanoparticles that increases drug delivery and accumulation in tumor tissue, can potentially
improve approaches in cancer therapy. Cisplatin-naproxen conjugate and corresponding
SBA-15 counterpart decreased the viability of B16 cells. Enlarged and elongated cells with
distinctly granular cytoplasm and the increased presence of lipid droplets were noticed
after haematoxylin–eosin and Oil Red O staining of treated cultures. In addition, enormous
nuclei and markedly heterochromatin foci were confirmed by PI staining indicating
establishment of senescent state upon the treatment. Alongside, differentiation of
melanoma cells toward melanocytes was demonstrated by elevated tyrosinase activity and
presence of melanin, thus leading to reduced tumorigenic potential in vivo. In addition,
cisplatin-naproxen conjugate and corresponding SBA-15 counterpart significantly reduced
melanoma growth in C57BL/6 mice, with lesser signs of toxicity compared to cisplatin as
a positive control. Strong antitumor potential of both, free and immobilized conjugates on
mouse melanoma cells opens numerous possibilities for further research.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia",
title = "Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model",
pages = "97-98",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6217"
}
Komazec, T., Mihajlović, E., Bovan, D., Mijatović, S., Predarska, I., Kaluđerović, G. N., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2023). Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model. in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
Belgrade: Faculty of Chemistry., 97-98.
https://hdl.handle.net/21.15107/rcub_ibiss_6217
Komazec T, Mihajlović E, Bovan D, Mijatović S, Predarska I, Kaluđerović GN, Hey-Hawkins E, Maksimović-Ivanić D. Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model. in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia. 2023;:97-98.
https://hdl.handle.net/21.15107/rcub_ibiss_6217 .
Komazec, Teodora, Mihajlović, Ekatarina, Bovan, Dijana, Mijatović, Sanja, Predarska, Ivana, Kaluđerović, Goran N., Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model" in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia (2023):97-98,
https://hdl.handle.net/21.15107/rcub_ibiss_6217 .

Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines

Predarska, Ivana; Saoud, Mohamad; Drača, Dijana; Morgan, Ibrahim; Komazec, Teodora; Eichhorn, Thomas; Mihajlović, Ekatarina; Dunđerović, Duško; Mijatović, Sanja; Maksimović-Ivanić, Danijela; Hey-Hawkins, Evamarie; Kaluđerović, Goran N.

(Basel: MDPI, 2022)

TY  - JOUR
AU  - Predarska, Ivana
AU  - Saoud, Mohamad
AU  - Drača, Dijana
AU  - Morgan, Ibrahim
AU  - Komazec, Teodora
AU  - Eichhorn, Thomas
AU  - Mihajlović, Ekatarina
AU  - Dunđerović, Duško
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
AU  - Kaluđerović, Goran N.
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5238
AB  - The main reasons for the limited clinical efficacy of the platinum(II)-based agent cisplatin
include drug resistance and significant side effects. Due to their better stability, as well as the
possibility to introduce biologically active ligands in their axial positions constructing multifunctional
prodrugs, creating platinum(IV) complexes is a tempting strategy for addressing these limitations.
Another strategy for developing chemotherapeutics with lower toxicity relies on the ability of
nanoparticles to accumulate in greater quantities in tumor tissues through passive targeting. To
combine the two approaches, three platinum(IV) conjugates based on a cisplatin scaffold containing
in the axial positions derivatives of caffeic and ferulic acid were prepared and loaded into SBA-
15 to produce the corresponding mesoporous silica nanoparticles (MSNs). The free platinum(IV)
conjugates demonstrated higher or comparable activity with respect to cisplatin against different
human breast cancer cell lines, while upon immobilization, superior antiproliferative activity with
markedly increased cytotoxicity (more than 1000-fold lower IC50 values) compared to cisplatin was
observed. Mechanistic investigations with the most potent conjugate, cisplatin-diacetyl caffeate (1),
and the corresponding MSNs (SBA-15|1) in a 4T1 mouse breast cancer cell line showed that these
compounds induce apoptotic cell death causing strong caspase activation. In vivo, in BALB/c mice,
1 and SBA-15|1 inhibited the tumor growth while decreasing the necrotic area and lowering the
mitotic rate.
PB  - Basel: MDPI
T2  - Nanomaterials
T1  - Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines
IS  - 21
VL  - 12
DO  - 10.3390/nano12213767
SP  - 3767
ER  - 
@article{
author = "Predarska, Ivana and Saoud, Mohamad and Drača, Dijana and Morgan, Ibrahim and Komazec, Teodora and Eichhorn, Thomas and Mihajlović, Ekatarina and Dunđerović, Duško and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie and Kaluđerović, Goran N.",
year = "2022",
abstract = "The main reasons for the limited clinical efficacy of the platinum(II)-based agent cisplatin
include drug resistance and significant side effects. Due to their better stability, as well as the
possibility to introduce biologically active ligands in their axial positions constructing multifunctional
prodrugs, creating platinum(IV) complexes is a tempting strategy for addressing these limitations.
Another strategy for developing chemotherapeutics with lower toxicity relies on the ability of
nanoparticles to accumulate in greater quantities in tumor tissues through passive targeting. To
combine the two approaches, three platinum(IV) conjugates based on a cisplatin scaffold containing
in the axial positions derivatives of caffeic and ferulic acid were prepared and loaded into SBA-
15 to produce the corresponding mesoporous silica nanoparticles (MSNs). The free platinum(IV)
conjugates demonstrated higher or comparable activity with respect to cisplatin against different
human breast cancer cell lines, while upon immobilization, superior antiproliferative activity with
markedly increased cytotoxicity (more than 1000-fold lower IC50 values) compared to cisplatin was
observed. Mechanistic investigations with the most potent conjugate, cisplatin-diacetyl caffeate (1),
and the corresponding MSNs (SBA-15|1) in a 4T1 mouse breast cancer cell line showed that these
compounds induce apoptotic cell death causing strong caspase activation. In vivo, in BALB/c mice,
1 and SBA-15|1 inhibited the tumor growth while decreasing the necrotic area and lowering the
mitotic rate.",
publisher = "Basel: MDPI",
journal = "Nanomaterials",
title = "Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines",
number = "21",
volume = "12",
doi = "10.3390/nano12213767",
pages = "3767"
}
Predarska, I., Saoud, M., Drača, D., Morgan, I., Komazec, T., Eichhorn, T., Mihajlović, E., Dunđerović, D., Mijatović, S., Maksimović-Ivanić, D., Hey-Hawkins, E.,& Kaluđerović, G. N.. (2022). Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines. in Nanomaterials
Basel: MDPI., 12(21), 3767.
https://doi.org/10.3390/nano12213767
Predarska I, Saoud M, Drača D, Morgan I, Komazec T, Eichhorn T, Mihajlović E, Dunđerović D, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E, Kaluđerović GN. Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines. in Nanomaterials. 2022;12(21):3767.
doi:10.3390/nano12213767 .
Predarska, Ivana, Saoud, Mohamad, Drača, Dijana, Morgan, Ibrahim, Komazec, Teodora, Eichhorn, Thomas, Mihajlović, Ekatarina, Dunđerović, Duško, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, Kaluđerović, Goran N., "Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines" in Nanomaterials, 12, no. 21 (2022):3767,
https://doi.org/10.3390/nano12213767 . .
1
10
9

Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate

Drača, Dijana; Predarska, Ivana; Komazec, Teodora; Mihajlović, Ekatarina; Kaluđerović, Goran N.; Mijatović, Sanja; Hey-Hawkins, Evamarie; Maksimović-Ivanić, Danijela

(Belgrade: Faculty of Chemistry, 2022)

TY  - CONF
AU  - Drača, Dijana
AU  - Predarska, Ivana
AU  - Komazec, Teodora
AU  - Mihajlović, Ekatarina
AU  - Kaluđerović, Goran N.
AU  - Mijatović, Sanja
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5288
AB  - Severe side effects and drug resistance are the main obstacles in clinical usage of cisplatin. The preparation of platinum(IV) prodrugs and the use of nanoparticles might be potential paths for overcoming the problem of toxicity. Caffeic acid is plant metabolite with many pharmacological effects such as antiinflammatory, anticancer, and hepatoprotective1. In this study, a hybrid molecule build up from cisplatin and acetylated caffeic acid, free and loaded into nanoparticles, SBA-15, was evaluated as an anticancer agent. Cytotoxic studies revealed that free conjugate possessed similar activity as cisplatin alone against 4T1 cell line, while upon imobilisation in SBA-15, much improved cytotoxicity was noticed. Further investigation showed that these compounds induced caspase-dependent apoptosis and an accumulation of cells in the subG compartment of the cell cycle. Intensive production of oxygen and nitrogen radicals was also observed. Also, survived clones lost their dividing potential. Mode of action of this cisplatin-caffeic acid conjugate against 4T1 cells makes it valuable in futher research, from the side of enhancement of its antitumour activity upon mobilisation into nanoparticles and potential reduced toxicity in vivo.
PB  - Belgrade: Faculty of Chemistry
C3  - Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
T1  - Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate
SP  - 62
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5288
ER  - 
@conference{
author = "Drača, Dijana and Predarska, Ivana and Komazec, Teodora and Mihajlović, Ekatarina and Kaluđerović, Goran N. and Mijatović, Sanja and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "Severe side effects and drug resistance are the main obstacles in clinical usage of cisplatin. The preparation of platinum(IV) prodrugs and the use of nanoparticles might be potential paths for overcoming the problem of toxicity. Caffeic acid is plant metabolite with many pharmacological effects such as antiinflammatory, anticancer, and hepatoprotective1. In this study, a hybrid molecule build up from cisplatin and acetylated caffeic acid, free and loaded into nanoparticles, SBA-15, was evaluated as an anticancer agent. Cytotoxic studies revealed that free conjugate possessed similar activity as cisplatin alone against 4T1 cell line, while upon imobilisation in SBA-15, much improved cytotoxicity was noticed. Further investigation showed that these compounds induced caspase-dependent apoptosis and an accumulation of cells in the subG compartment of the cell cycle. Intensive production of oxygen and nitrogen radicals was also observed. Also, survived clones lost their dividing potential. Mode of action of this cisplatin-caffeic acid conjugate against 4T1 cells makes it valuable in futher research, from the side of enhancement of its antitumour activity upon mobilisation into nanoparticles and potential reduced toxicity in vivo.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia",
title = "Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate",
pages = "62",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5288"
}
Drača, D., Predarska, I., Komazec, T., Mihajlović, E., Kaluđerović, G. N., Mijatović, S., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2022). Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
Belgrade: Faculty of Chemistry., 62.
https://hdl.handle.net/21.15107/rcub_ibiss_5288
Drača D, Predarska I, Komazec T, Mihajlović E, Kaluđerović GN, Mijatović S, Hey-Hawkins E, Maksimović-Ivanić D. Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:62.
https://hdl.handle.net/21.15107/rcub_ibiss_5288 .
Drača, Dijana, Predarska, Ivana, Komazec, Teodora, Mihajlović, Ekatarina, Kaluđerović, Goran N., Mijatović, Sanja, Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):62,
https://hdl.handle.net/21.15107/rcub_ibiss_5288 .

Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15

Mihajlović, Ekatarina; Drača, Dijana; Komazec, Teodora; Mijatović, Sanja; Predarska, Ivana; Kaluđerović, Goran N.; Hey-Hawkins, Evamarie; Maksimović-Ivanić, Danijela

(Belgrade: Faculty of Chemistry, 2022)

TY  - CONF
AU  - Mihajlović, Ekatarina
AU  - Drača, Dijana
AU  - Komazec, Teodora
AU  - Mijatović, Sanja
AU  - Predarska, Ivana
AU  - Kaluđerović, Goran N.
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5287
AB  - To develop anticancer drugs with higher activity and reduced toxicity, cisplatin was used as a scaffold to bear the anti-inflammatory drug naproxen and this conjugate was loaded into silica nanoparticles, SBA-15. In this study, the cytotoxic effect of the free conjugate and the one loaded in SBA-15 was evaluated on different cancer cell lines of mouse origin (B16, 4T1, CT26 and MC38). Treatment with free, as well as with SBA-15-bound conjugate, dose-dependently decreased viability of all cancer cell lines. The viability decrease of B16 cells after treatment with both agents was not caused by apoptosis, but it was followed by caspase activation. On the other hand, treatment with both agents caused significant decrease of B16 cells division rate, indicating the primary cytostatic effect of these agents. Additionally, it was shown that treatment with the free conjugate caused intensified autophagy, while the conjugate loaded into SBA-15 did not show this effect. Since the viability of cells recovered upon the exposure to 3-methyl adenine, detected autophagy serves as a cell death mechanism. Overall, these results indicate that both nacked and immobilized conjugates show great potential for cancer treatment.
PB  - Belgrade: Faculty of Chemistry
C3  - Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
T1  - Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15
SP  - 99
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5287
ER  - 
@conference{
author = "Mihajlović, Ekatarina and Drača, Dijana and Komazec, Teodora and Mijatović, Sanja and Predarska, Ivana and Kaluđerović, Goran N. and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "To develop anticancer drugs with higher activity and reduced toxicity, cisplatin was used as a scaffold to bear the anti-inflammatory drug naproxen and this conjugate was loaded into silica nanoparticles, SBA-15. In this study, the cytotoxic effect of the free conjugate and the one loaded in SBA-15 was evaluated on different cancer cell lines of mouse origin (B16, 4T1, CT26 and MC38). Treatment with free, as well as with SBA-15-bound conjugate, dose-dependently decreased viability of all cancer cell lines. The viability decrease of B16 cells after treatment with both agents was not caused by apoptosis, but it was followed by caspase activation. On the other hand, treatment with both agents caused significant decrease of B16 cells division rate, indicating the primary cytostatic effect of these agents. Additionally, it was shown that treatment with the free conjugate caused intensified autophagy, while the conjugate loaded into SBA-15 did not show this effect. Since the viability of cells recovered upon the exposure to 3-methyl adenine, detected autophagy serves as a cell death mechanism. Overall, these results indicate that both nacked and immobilized conjugates show great potential for cancer treatment.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia",
title = "Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15",
pages = "99",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5287"
}
Mihajlović, E., Drača, D., Komazec, T., Mijatović, S., Predarska, I., Kaluđerović, G. N., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2022). Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
Belgrade: Faculty of Chemistry., 99.
https://hdl.handle.net/21.15107/rcub_ibiss_5287
Mihajlović E, Drača D, Komazec T, Mijatović S, Predarska I, Kaluđerović GN, Hey-Hawkins E, Maksimović-Ivanić D. Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:99.
https://hdl.handle.net/21.15107/rcub_ibiss_5287 .
Mihajlović, Ekatarina, Drača, Dijana, Komazec, Teodora, Mijatović, Sanja, Predarska, Ivana, Kaluđerović, Goran N., Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):99,
https://hdl.handle.net/21.15107/rcub_ibiss_5287 .

Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines

Komazec, Teodora; Drača, Dijana; Mijatović, Sanja; Predarska, Ivana; Kaluđerović, Goran N.; Hey-Hawkins, Evamarie; Maksimović-Ivanić, Danijela

(Belgrade: Faculty of Chemistry, 2022)

TY  - CONF
AU  - Komazec, Teodora
AU  - Drača, Dijana
AU  - Mijatović, Sanja
AU  - Predarska, Ivana
AU  - Kaluđerović, Goran N.
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5284
AB  - From its discovery, cisplatin therapy has widely been associated with toxicity and severe side effects. Platinum(IV) complexes, as well as immobilising them in nanomaterials could help to overcome these problems. Cyclooxygenase-2 (COX-2) is involved in cancer progresssion,1 which encourages the development of inhibitors of COX enzymes in antitumour therapy. To determine the potential cytotoxic effect, a cisplatin-ibuprofen conjugate in free form, as well as loaded into SBA-15 nanomaterial, was tested on 4T1, CT26, B16 and MC38 cell lines. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and crystal violet viability assays showed that both agents dose-dependently decreased the number of viable cells of all tested cell lines. Flow cytometric analysis revealed significant decrease in the division potential of B16-treated cells. In further investigations, activation of caspases proved by ApoStat assay was noticed; however, apoptosis was not identified by flow cytometry in culture of treated B16 cells. Finally, light microscopy evaluation revealed the presence of enlarged cells with prominent heterochromatin foci in nuclei upon the treatment indicating that cells entered senescent state. High antitumour potential defined at the nanomolar concentration on mouse melanoma cells make cisplatin-ibuprofen a suitable candidate for further research.
PB  - Belgrade: Faculty of Chemistry
C3  - Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
T1  - Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines
SP  - 83
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5284
ER  - 
@conference{
author = "Komazec, Teodora and Drača, Dijana and Mijatović, Sanja and Predarska, Ivana and Kaluđerović, Goran N. and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "From its discovery, cisplatin therapy has widely been associated with toxicity and severe side effects. Platinum(IV) complexes, as well as immobilising them in nanomaterials could help to overcome these problems. Cyclooxygenase-2 (COX-2) is involved in cancer progresssion,1 which encourages the development of inhibitors of COX enzymes in antitumour therapy. To determine the potential cytotoxic effect, a cisplatin-ibuprofen conjugate in free form, as well as loaded into SBA-15 nanomaterial, was tested on 4T1, CT26, B16 and MC38 cell lines. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and crystal violet viability assays showed that both agents dose-dependently decreased the number of viable cells of all tested cell lines. Flow cytometric analysis revealed significant decrease in the division potential of B16-treated cells. In further investigations, activation of caspases proved by ApoStat assay was noticed; however, apoptosis was not identified by flow cytometry in culture of treated B16 cells. Finally, light microscopy evaluation revealed the presence of enlarged cells with prominent heterochromatin foci in nuclei upon the treatment indicating that cells entered senescent state. High antitumour potential defined at the nanomolar concentration on mouse melanoma cells make cisplatin-ibuprofen a suitable candidate for further research.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia",
title = "Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines",
pages = "83",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5284"
}
Komazec, T., Drača, D., Mijatović, S., Predarska, I., Kaluđerović, G. N., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2022). Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
Belgrade: Faculty of Chemistry., 83.
https://hdl.handle.net/21.15107/rcub_ibiss_5284
Komazec T, Drača D, Mijatović S, Predarska I, Kaluđerović GN, Hey-Hawkins E, Maksimović-Ivanić D. Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:83.
https://hdl.handle.net/21.15107/rcub_ibiss_5284 .
Komazec, Teodora, Drača, Dijana, Mijatović, Sanja, Predarska, Ivana, Kaluđerović, Goran N., Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):83,
https://hdl.handle.net/21.15107/rcub_ibiss_5284 .