TY  - JOUR
AU  - Markelić, Milica
AU  - Mojić, Marija
AU  - Bovan, Dijana
AU  - Jelača, Sanja
AU  - Jović, Zorana
AU  - Purić, Milica
AU  - Koruga, Djuro
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5470
AB  - In our recent study, we showed that in vitro treatment of melanoma cells with hyperpolarized light (HPL) as well as with the second derivative of fullerene, hyper-harmonized hydroxylated fullerene water complex (3HFWC) reduced viability of cells by decreasing their proliferative capacity and inducing senescence and reprogramming towards a normal, melanocytic phenotype. Therefore, we wanted to determine whether these effects persisted in vivo in the syngeneic mouse melanoma model with a combined treatment of HPL irradiation and 3HFWC per os. Our results demonstrated the potent antitumor effects of 3HFWC nanosubstance assisted by HPL irradiation. These effects were primarily driven by the stimulation of melanoma cell growth arrest, the establishment of a senescent phenotype, and melanocytic differentiation on the one hand, and the awakening of the antitumor immune response on the other. In addition, the combined treatment reduced the protumorigenic activity of immune cells by depleting T regulatory cells, myeloid-derived suppressors, and M2 macrophages. The support of the 3HFWC substance by HPL irradiation may be the axis of the new approach design based on tumor cell reprogramming synchronized with the mobilization of the host’s protective immune response.
PB  - Basel: MDPI
T2  - Nanomaterials
T1  - Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo
IS  - 3
VL  - 13
DO  - 10.3390/nano13030372
SP  - 372
ER  - 

@article{
author = "Markelić, Milica and Mojić, Marija and Bovan, Dijana and Jelača, Sanja and Jović, Zorana and Purić, Milica and Koruga, Djuro and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "In our recent study, we showed that in vitro treatment of melanoma cells with hyperpolarized light (HPL) as well as with the second derivative of fullerene, hyper-harmonized hydroxylated fullerene water complex (3HFWC) reduced viability of cells by decreasing their proliferative capacity and inducing senescence and reprogramming towards a normal, melanocytic phenotype. Therefore, we wanted to determine whether these effects persisted in vivo in the syngeneic mouse melanoma model with a combined treatment of HPL irradiation and 3HFWC per os. Our results demonstrated the potent antitumor effects of 3HFWC nanosubstance assisted by HPL irradiation. These effects were primarily driven by the stimulation of melanoma cell growth arrest, the establishment of a senescent phenotype, and melanocytic differentiation on the one hand, and the awakening of the antitumor immune response on the other. In addition, the combined treatment reduced the protumorigenic activity of immune cells by depleting T regulatory cells, myeloid-derived suppressors, and M2 macrophages. The support of the 3HFWC substance by HPL irradiation may be the axis of the new approach design based on tumor cell reprogramming synchronized with the mobilization of the host’s protective immune response.",
publisher = "Basel: MDPI",
journal = "Nanomaterials",
title = "Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo",
number = "3",
volume = "13",
doi = "10.3390/nano13030372",
pages = "372"
}

Markelić, M., Mojić, M., Bovan, D., Jelača, S., Jović, Z., Purić, M., Koruga, D., Mijatović, S.,& Maksimović-Ivanić, D.. (2023). Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo. in Nanomaterials
Basel: MDPI., 13(3), 372.
https://doi.org/10.3390/nano13030372

Markelić M, Mojić M, Bovan D, Jelača S, Jović Z, Purić M, Koruga D, Mijatović S, Maksimović-Ivanić D. Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo. in Nanomaterials. 2023;13(3):372.
doi:10.3390/nano13030372 .

Markelić, Milica, Mojić, Marija, Bovan, Dijana, Jelača, Sanja, Jović, Zorana, Purić, Milica, Koruga, Djuro, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo" in Nanomaterials, 13, no. 3 (2023):372,
https://doi.org/10.3390/nano13030372 . .

TY  - JOUR
AU  - Markelić, Milica
AU  - Drača, Dijana
AU  - Krajnović, Tamara
AU  - Jović, Zorana
AU  - Vuksanović, Milica
AU  - Koruga, Djuro
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4953
AB  - (1) Background: Their unique structure and electron deficiency have brought fullerenes
into the focus of research in many fields, including medicine. The hyper-harmonized hydroxylated
fullerene water complex (3HFWC) formulation has solved the limitations of the poor solubility
and bioavailability of fullerenes. To achieve better antitumor activity, 3HFWC was combined with
short-term irradiation of cells with hyperpolarized light (HPL) generated by the application of a
nanophotonic fullerene filter in a Bioptron® device. The benefits of HPL were confirmed in the
microcirculation, wound healing and immunological function. (2) Methods: B16, B16-F10 and A375
melanoma cells were exposed to a wide spectrum of 3HFWC doses and to a single short-term HPL
irradiation. (3) Results: Apart from the differences in the redox status and level of invasiveness, the
effects of the treatments were quite similar. Decreased viability, morphological alteration, signs of
melanocytic differentiation and cellular senescence were observed upon the successful internalization
of the nanoquantum substance. (4) Conclusions: Overall, 3HFWC/HPL promoted melanoma cell
reprogramming toward a normal phenotype.
PB  - Basel: MDPI
T2  - Nanomaterials (Basel)
T1  - Combined Action of Hyper-Harmonized Hydroxylated Fullerene Water Complex and Hyperpolarized Light Leads to Melanoma Cell Reprogramming In Vitro
IS  - 8
VL  - 12
DO  - 10.3390/nano12081331
SP  - 1331
ER  - 

@article{
author = "Markelić, Milica and Drača, Dijana and Krajnović, Tamara and Jović, Zorana and Vuksanović, Milica and Koruga, Djuro and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "(1) Background: Their unique structure and electron deficiency have brought fullerenes
into the focus of research in many fields, including medicine. The hyper-harmonized hydroxylated
fullerene water complex (3HFWC) formulation has solved the limitations of the poor solubility
and bioavailability of fullerenes. To achieve better antitumor activity, 3HFWC was combined with
short-term irradiation of cells with hyperpolarized light (HPL) generated by the application of a
nanophotonic fullerene filter in a Bioptron® device. The benefits of HPL were confirmed in the
microcirculation, wound healing and immunological function. (2) Methods: B16, B16-F10 and A375
melanoma cells were exposed to a wide spectrum of 3HFWC doses and to a single short-term HPL
irradiation. (3) Results: Apart from the differences in the redox status and level of invasiveness, the
effects of the treatments were quite similar. Decreased viability, morphological alteration, signs of
melanocytic differentiation and cellular senescence were observed upon the successful internalization
of the nanoquantum substance. (4) Conclusions: Overall, 3HFWC/HPL promoted melanoma cell
reprogramming toward a normal phenotype.",
publisher = "Basel: MDPI",
journal = "Nanomaterials (Basel)",
title = "Combined Action of Hyper-Harmonized Hydroxylated Fullerene Water Complex and Hyperpolarized Light Leads to Melanoma Cell Reprogramming In Vitro",
number = "8",
volume = "12",
doi = "10.3390/nano12081331",
pages = "1331"
}

Markelić, M., Drača, D., Krajnović, T., Jović, Z., Vuksanović, M., Koruga, D., Mijatović, S.,& Maksimović-Ivanić, D.. (2022). Combined Action of Hyper-Harmonized Hydroxylated Fullerene Water Complex and Hyperpolarized Light Leads to Melanoma Cell Reprogramming In Vitro. in Nanomaterials (Basel)
Basel: MDPI., 12(8), 1331.
https://doi.org/10.3390/nano12081331

Markelić M, Drača D, Krajnović T, Jović Z, Vuksanović M, Koruga D, Mijatović S, Maksimović-Ivanić D. Combined Action of Hyper-Harmonized Hydroxylated Fullerene Water Complex and Hyperpolarized Light Leads to Melanoma Cell Reprogramming In Vitro. in Nanomaterials (Basel). 2022;12(8):1331.
doi:10.3390/nano12081331 .

Markelić, Milica, Drača, Dijana, Krajnović, Tamara, Jović, Zorana, Vuksanović, Milica, Koruga, Djuro, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Combined Action of Hyper-Harmonized Hydroxylated Fullerene Water Complex and Hyperpolarized Light Leads to Melanoma Cell Reprogramming In Vitro" in Nanomaterials (Basel), 12, no. 8 (2022):1331,
https://doi.org/10.3390/nano12081331 . .

TY  - CONF
AU  - Golić, Igor
AU  - Krajnović, Tamara
AU  - Jelača, Sanja
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Koruga, Đuro
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5296
AB  - Fullerene C60 is the third allotropic modification of carbon in nature. Exceptional physical and
structural features of C60 molecule make it attractive for biomedical research in a wide spectrum of
applications from imaging, drug delivery, to therapy of different disorders. However, its low
solubility in water or polar solvents, and genotoxic potential represent serious barriers for its usage.
To overcome mentioned limits the second derivative of fullerene C60 (Hyper harmonized
hydroxylated fullerene water complex - 3HFWC) is created through functionalization of the first
fullerene C60 derivative (fullerol - C60(OH)x) by the addition of paired OH groups in water layers
surrounding the solid phase of substance. The solid phase consists of the C60 molecule, covalent OH
groups and 3-6 water layers with strong hydrogen bonds. The liquid phase consists of additional
water layers bonded by moderate to weak hydrogen bonds. In addition, the third derivative of
fullerene is made when 3HFWC was integrated with nano-gold particles (nAu@3HFWC). The aim
of this study was to evaluate fullerene C60 derivatives uptake and their intracellular distribution in
mouse 3T3 fibroblasts. Cells were exposed to 30 μg/ml C60(OH)x, or 30 μg/ml 3HFWC, or 5μg/ml
nAu@3HFWC during 30 min, 1h or 2h and analysis was done by Philips FEI CM12 transmission
electron microscope. Ultrastructural analysis showed mainly cytoplasmic localization of C60(OH)x
and its derivatives, and also a sporadic presence in mitochondria and nuclei. The concentration of
fullerene derivatives in these cells was time-dependent, i.e., more concentration was observed in
cells with longer exposition to these fullerenes. Furthermore, C60(OH)x is also localized in lysosomes
in higher concentrations. These results suggest that novel C60 fullerene derivatives show better
biocompatibility in mouse 3T3 fibroblasts compared to C60(OH)x, which mainly ends in lysosomes,
the waste disposal system of the cell.
PB  - Belgrade: Serbian Academy of Sciences and Arts
C3  - Program and Book of Abstracts: Second International Conference ELMINA; 2022 Aug 22-26. Belgrade, Serbia
T1  - Investigation of the Action of the Fullerene (C60) Derivatives on Mouse 3T3 Fibroblast Cell Lines
SP  - 84
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5296
ER  - 

@conference{
author = "Golić, Igor and Krajnović, Tamara and Jelača, Sanja and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Koruga, Đuro",
year = "2022",
abstract = "Fullerene C60 is the third allotropic modification of carbon in nature. Exceptional physical and
structural features of C60 molecule make it attractive for biomedical research in a wide spectrum of
applications from imaging, drug delivery, to therapy of different disorders. However, its low
solubility in water or polar solvents, and genotoxic potential represent serious barriers for its usage.
To overcome mentioned limits the second derivative of fullerene C60 (Hyper harmonized
hydroxylated fullerene water complex - 3HFWC) is created through functionalization of the first
fullerene C60 derivative (fullerol - C60(OH)x) by the addition of paired OH groups in water layers
surrounding the solid phase of substance. The solid phase consists of the C60 molecule, covalent OH
groups and 3-6 water layers with strong hydrogen bonds. The liquid phase consists of additional
water layers bonded by moderate to weak hydrogen bonds. In addition, the third derivative of
fullerene is made when 3HFWC was integrated with nano-gold particles (nAu@3HFWC). The aim
of this study was to evaluate fullerene C60 derivatives uptake and their intracellular distribution in
mouse 3T3 fibroblasts. Cells were exposed to 30 μg/ml C60(OH)x, or 30 μg/ml 3HFWC, or 5μg/ml
nAu@3HFWC during 30 min, 1h or 2h and analysis was done by Philips FEI CM12 transmission
electron microscope. Ultrastructural analysis showed mainly cytoplasmic localization of C60(OH)x
and its derivatives, and also a sporadic presence in mitochondria and nuclei. The concentration of
fullerene derivatives in these cells was time-dependent, i.e., more concentration was observed in
cells with longer exposition to these fullerenes. Furthermore, C60(OH)x is also localized in lysosomes
in higher concentrations. These results suggest that novel C60 fullerene derivatives show better
biocompatibility in mouse 3T3 fibroblasts compared to C60(OH)x, which mainly ends in lysosomes,
the waste disposal system of the cell.",
publisher = "Belgrade: Serbian Academy of Sciences and Arts",
journal = "Program and Book of Abstracts: Second International Conference ELMINA; 2022 Aug 22-26. Belgrade, Serbia",
title = "Investigation of the Action of the Fullerene (C60) Derivatives on Mouse 3T3 Fibroblast Cell Lines",
pages = "84",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5296"
}

Golić, I., Krajnović, T., Jelača, S., Mijatović, S., Maksimović-Ivanić, D.,& Koruga, Đ.. (2022). Investigation of the Action of the Fullerene (C60) Derivatives on Mouse 3T3 Fibroblast Cell Lines. in Program and Book of Abstracts: Second International Conference ELMINA; 2022 Aug 22-26. Belgrade, Serbia
Belgrade: Serbian Academy of Sciences and Arts., 84.
https://hdl.handle.net/21.15107/rcub_ibiss_5296

Golić I, Krajnović T, Jelača S, Mijatović S, Maksimović-Ivanić D, Koruga Đ. Investigation of the Action of the Fullerene (C60) Derivatives on Mouse 3T3 Fibroblast Cell Lines. in Program and Book of Abstracts: Second International Conference ELMINA; 2022 Aug 22-26. Belgrade, Serbia. 2022;:84.
https://hdl.handle.net/21.15107/rcub_ibiss_5296 .

Golić, Igor, Krajnović, Tamara, Jelača, Sanja, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Koruga, Đuro, "Investigation of the Action of the Fullerene (C60) Derivatives on Mouse 3T3 Fibroblast Cell Lines" in Program and Book of Abstracts: Second International Conference ELMINA; 2022 Aug 22-26. Belgrade, Serbia (2022):84,
https://hdl.handle.net/21.15107/rcub_ibiss_5296 .

TY  - CONF
AU  - Markelić, Milica
AU  - Mojić, Marija
AU  - Drača, Dijana
AU  - Jelača, Sanja
AU  - Koruga, Djuro
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5285
AB  - Antioxidant and anticancer properties of fullerene C60 and especially of its polyhydroxylated, water soluble derivatives (fullerols) make them appealing for biomedical applications. In order to analyse antitumor effects of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC)1, second generation of fullerol, melanoma cells of different intracellular features and invasive potential (B16, B16-F10, A375) were treated with 3HFWC in various concentrations (0.19-100 μg/ml) for 24, 48 and 72h. Subsequently, syngeneic murine melanoma model was used (oral 3HFWC intake, 0.15 g/l). The most prominent effect of 3HFWC, both in vitro and in vivo2, was induction of cell senescence, followed by decreased proliferative capacity and tumor growth inhibition. Senescent cells remained viable in vitro, but lost ability to divide and decreased metabolic activity, due to mitochondria alterations. Our findings demonstrate pro-senescence approach in antitumor therapy which is suggested to be less aggressive than the conventional strategies based on cancer cell killing, frequently followed by compensatory proliferation and subsequent tumor progression.
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  - Pro-senescent effects of hyper-harmonized hydroxylated fullerene water complex in melanoma
SP  - 95
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5285
ER  - 

@conference{
author = "Markelić, Milica and Mojić, Marija and Drača, Dijana and Jelača, Sanja and Koruga, Djuro and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "Antioxidant and anticancer properties of fullerene C60 and especially of its polyhydroxylated, water soluble derivatives (fullerols) make them appealing for biomedical applications. In order to analyse antitumor effects of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC)1, second generation of fullerol, melanoma cells of different intracellular features and invasive potential (B16, B16-F10, A375) were treated with 3HFWC in various concentrations (0.19-100 μg/ml) for 24, 48 and 72h. Subsequently, syngeneic murine melanoma model was used (oral 3HFWC intake, 0.15 g/l). The most prominent effect of 3HFWC, both in vitro and in vivo2, was induction of cell senescence, followed by decreased proliferative capacity and tumor growth inhibition. Senescent cells remained viable in vitro, but lost ability to divide and decreased metabolic activity, due to mitochondria alterations. Our findings demonstrate pro-senescence approach in antitumor therapy which is suggested to be less aggressive than the conventional strategies based on cancer cell killing, frequently followed by compensatory proliferation and subsequent tumor progression.",
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 = "Pro-senescent effects of hyper-harmonized hydroxylated fullerene water complex in melanoma",
pages = "95",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5285"
}

Markelić, M., Mojić, M., Drača, D., Jelača, S., Koruga, D., Mijatović, S.,& Maksimović-Ivanić, D.. (2022). Pro-senescent effects of hyper-harmonized hydroxylated fullerene water complex in melanoma. 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., 95.
https://hdl.handle.net/21.15107/rcub_ibiss_5285

Markelić M, Mojić M, Drača D, Jelača S, Koruga D, Mijatović S, Maksimović-Ivanić D. Pro-senescent effects of hyper-harmonized hydroxylated fullerene water complex in melanoma. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:95.
https://hdl.handle.net/21.15107/rcub_ibiss_5285 .

Markelić, Milica, Mojić, Marija, Drača, Dijana, Jelača, Sanja, Koruga, Djuro, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Pro-senescent effects of hyper-harmonized hydroxylated fullerene water complex in melanoma" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):95,
https://hdl.handle.net/21.15107/rcub_ibiss_5285 .