TY  - CONF
AU  - Pantović Pavlović, Marijana
AU  - Pavlović, Miroslav
AU  - Nikolić, Nebojša D.
AU  - Kojić, Vesna V.
AU  - Stevanović, Jasmina
AU  - Panić, Vladimir
AU  - Ignjatović, Nenad
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/6561
AB  - Calcium phosphates (CP), amongst which amorphous calcium phosphate (ACP) and hydroxyapatite (HAp), along with Ti and TiO2 layers, have found vast applications in preventive and regenerative medicine due to their excellent biocompatibility, nontoxic properties and ability to participate in the normal metabolism of organisms. In this paper cytotoxicity of amorphous calcium phosphate (ACP) and chitosan lactate (ChOL) multifunctional and hybrid composite coatings on MRC-5 human lung fibroblast cell line is presented. ACP/TiO2 and ACP/TiO2/ChOL are deposited by coatings new in situ anodization/anaphoretic deposition process at constant voltage of 60 V for 180 s at 25 °C. Cytotoxicity tests showed that there was no significant decrease in the survival of healthy MRC-5 cells in the Ti and ACP/TiO2 composite samples, while there was an increase in the number of viable cells in the ACP/TiO2/ChOL sample. There is improved cell proliferation, differentiation and cell viability in the later. Sample containing ACP/TiO2/ChOL coating showed negative cytotoxicity in both DET and MTT tests. Greater recovery of MRC-5 human lung fibroblasts cells was observed compared to the control sample after 48 h of recovery. From these results, it can be concluded that not only the ACP/TiO2/ChOL multifunctional composite coating is non-cytotoxic, but the presence of ChOL in the coating improves cell proliferation, differentiation and cell viability. Based on the obtained results, it can be concluded that both composite materials used in the studies are non-cytotoxic to the cell lines used, and that 5 wt.% of ChOL has a positive effect on the non-toxicity of the material. Based on presented results in this paper and previous published results of the physicochemical and bioactive properties of the ACP/TiO2/ChOL composite material, it can be concluded that further development as well as potential preclinical studies would be largely justified.
PB  - Zvornik : Faculty of Technology
C3  - Book of Abstracts - VII International Congress Engineering, Environment and Materials in Process Industry, March 17-19, 2021, Jahorina, Republic of Srpska, Bosnia and Herzegovina
T1  - Cytotoxicity of Multifunctional Composites of Amorphous Calcium Phosphate Containing Chitosan on Titanium Obtained by Novel in Situ Anodic Process
SP  - 230
EP  - 230
UR  - https://hdl.handle.net/21.15107/rcub_cer_6561
ER  - 

@conference{
author = "Pantović Pavlović, Marijana and Pavlović, Miroslav and Nikolić, Nebojša D. and Kojić, Vesna V. and Stevanović, Jasmina and Panić, Vladimir and Ignjatović, Nenad",
year = "2021",
abstract = "Calcium phosphates (CP), amongst which amorphous calcium phosphate (ACP) and hydroxyapatite (HAp), along with Ti and TiO2 layers, have found vast applications in preventive and regenerative medicine due to their excellent biocompatibility, nontoxic properties and ability to participate in the normal metabolism of organisms. In this paper cytotoxicity of amorphous calcium phosphate (ACP) and chitosan lactate (ChOL) multifunctional and hybrid composite coatings on MRC-5 human lung fibroblast cell line is presented. ACP/TiO2 and ACP/TiO2/ChOL are deposited by coatings new in situ anodization/anaphoretic deposition process at constant voltage of 60 V for 180 s at 25 °C. Cytotoxicity tests showed that there was no significant decrease in the survival of healthy MRC-5 cells in the Ti and ACP/TiO2 composite samples, while there was an increase in the number of viable cells in the ACP/TiO2/ChOL sample. There is improved cell proliferation, differentiation and cell viability in the later. Sample containing ACP/TiO2/ChOL coating showed negative cytotoxicity in both DET and MTT tests. Greater recovery of MRC-5 human lung fibroblasts cells was observed compared to the control sample after 48 h of recovery. From these results, it can be concluded that not only the ACP/TiO2/ChOL multifunctional composite coating is non-cytotoxic, but the presence of ChOL in the coating improves cell proliferation, differentiation and cell viability. Based on the obtained results, it can be concluded that both composite materials used in the studies are non-cytotoxic to the cell lines used, and that 5 wt.% of ChOL has a positive effect on the non-toxicity of the material. Based on presented results in this paper and previous published results of the physicochemical and bioactive properties of the ACP/TiO2/ChOL composite material, it can be concluded that further development as well as potential preclinical studies would be largely justified.",
publisher = "Zvornik : Faculty of Technology",
journal = "Book of Abstracts - VII International Congress Engineering, Environment and Materials in Process Industry, March 17-19, 2021, Jahorina, Republic of Srpska, Bosnia and Herzegovina",
title = "Cytotoxicity of Multifunctional Composites of Amorphous Calcium Phosphate Containing Chitosan on Titanium Obtained by Novel in Situ Anodic Process",
pages = "230-230",
url = "https://hdl.handle.net/21.15107/rcub_cer_6561"
}

Pantović Pavlović, M., Pavlović, M., Nikolić, N. D., Kojić, V. V., Stevanović, J., Panić, V.,& Ignjatović, N.. (2021). Cytotoxicity of Multifunctional Composites of Amorphous Calcium Phosphate Containing Chitosan on Titanium Obtained by Novel in Situ Anodic Process. in Book of Abstracts - VII International Congress Engineering, Environment and Materials in Process Industry, March 17-19, 2021, Jahorina, Republic of Srpska, Bosnia and Herzegovina
Zvornik : Faculty of Technology., 230-230.
https://hdl.handle.net/21.15107/rcub_cer_6561

Pantović Pavlović M, Pavlović M, Nikolić ND, Kojić VV, Stevanović J, Panić V, Ignjatović N. Cytotoxicity of Multifunctional Composites of Amorphous Calcium Phosphate Containing Chitosan on Titanium Obtained by Novel in Situ Anodic Process. in Book of Abstracts - VII International Congress Engineering, Environment and Materials in Process Industry, March 17-19, 2021, Jahorina, Republic of Srpska, Bosnia and Herzegovina. 2021;:230-230.
https://hdl.handle.net/21.15107/rcub_cer_6561 .

Pantović Pavlović, Marijana, Pavlović, Miroslav, Nikolić, Nebojša D., Kojić, Vesna V., Stevanović, Jasmina, Panić, Vladimir, Ignjatović, Nenad, "Cytotoxicity of Multifunctional Composites of Amorphous Calcium Phosphate Containing Chitosan on Titanium Obtained by Novel in Situ Anodic Process" in Book of Abstracts - VII International Congress Engineering, Environment and Materials in Process Industry, March 17-19, 2021, Jahorina, Republic of Srpska, Bosnia and Herzegovina (2021):230-230,
https://hdl.handle.net/21.15107/rcub_cer_6561 .

TY  - JOUR
AU  - Gajić, Mihajlo
AU  - Ilić, Budimir S.
AU  - Bondžić, Bojan
AU  - Džambaski, Zdravko
AU  - Kojić, Vesna V.
AU  - Jakimov, Dimitar S.
AU  - Kocić, Gordana
AU  - Šmelcerović, Andrija
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4815
AB  - Herein we report an assessment of 24 1,2,3,4-tetrahydroisoquinoline derivatives for potential DNase I (deoxyribonuclease I) inhibitory properties in vitro. Four of them inhibited DNase I with IC50 values below 200 μM. The most potent was 1-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)propan-2-one (2) (IC50=134.35±11.38 μM) exhibiting slightly better IC50 value compared to three other active compounds, 2-[2-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]-1-phenylethan-1-one (15) (IC50=147.51±14.87 μM), 2-[2-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]cyclohexan-1-one (18) (IC50=149.07±2.98 μM) and 2-[6,7-dimethoxy-2-(p-tolyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]cyclohexan-1-one (22) (IC50=148.31±2.96 μM). Cytotoxicity assessment of the active DNase I inhibitors revealed a lack of toxic effects on the healthy cell lines MRC-5. Molecular docking and molecular dynamics simulations suggest that interactions with Glu 39, His 134, Asn 170, Tyr 211, Asp 251 and His 252 are an important factor for inhibitors affinity toward the DNase I. Observed interactions would be beneficial for the discovery of new active 1,2,3,4-tetrahydroisoquinoline-based inhibitors of DNase I, but might also encourage researchers to further explore and utilize potential therapeutic application of DNase I inhibitors, based on a versatile role of DNase I during apoptotic cell death.
PB  - Wiley
T2  - Chemistry and Biodisversity
T1  - 1,2,3,4-Tetrahydroisoquinoline Derivatives as a Novel Deoxyribonuclease I Inhibitors
VL  - 18
IS  - 8
SP  - e2100261
DO  - 10.1002/cbdv.202100261
ER  - 

@article{
author = "Gajić, Mihajlo and Ilić, Budimir S. and Bondžić, Bojan and Džambaski, Zdravko and Kojić, Vesna V. and Jakimov, Dimitar S. and Kocić, Gordana and Šmelcerović, Andrija",
year = "2021",
abstract = "Herein we report an assessment of 24 1,2,3,4-tetrahydroisoquinoline derivatives for potential DNase I (deoxyribonuclease I) inhibitory properties in vitro. Four of them inhibited DNase I with IC50 values below 200 μM. The most potent was 1-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)propan-2-one (2) (IC50=134.35±11.38 μM) exhibiting slightly better IC50 value compared to three other active compounds, 2-[2-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]-1-phenylethan-1-one (15) (IC50=147.51±14.87 μM), 2-[2-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]cyclohexan-1-one (18) (IC50=149.07±2.98 μM) and 2-[6,7-dimethoxy-2-(p-tolyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]cyclohexan-1-one (22) (IC50=148.31±2.96 μM). Cytotoxicity assessment of the active DNase I inhibitors revealed a lack of toxic effects on the healthy cell lines MRC-5. Molecular docking and molecular dynamics simulations suggest that interactions with Glu 39, His 134, Asn 170, Tyr 211, Asp 251 and His 252 are an important factor for inhibitors affinity toward the DNase I. Observed interactions would be beneficial for the discovery of new active 1,2,3,4-tetrahydroisoquinoline-based inhibitors of DNase I, but might also encourage researchers to further explore and utilize potential therapeutic application of DNase I inhibitors, based on a versatile role of DNase I during apoptotic cell death.",
publisher = "Wiley",
journal = "Chemistry and Biodisversity",
title = "1,2,3,4-Tetrahydroisoquinoline Derivatives as a Novel Deoxyribonuclease I Inhibitors",
volume = "18",
number = "8",
pages = "e2100261",
doi = "10.1002/cbdv.202100261"
}

Gajić, M., Ilić, B. S., Bondžić, B., Džambaski, Z., Kojić, V. V., Jakimov, D. S., Kocić, G.,& Šmelcerović, A.. (2021). 1,2,3,4-Tetrahydroisoquinoline Derivatives as a Novel Deoxyribonuclease I Inhibitors. in Chemistry and Biodisversity
Wiley., 18(8), e2100261.
https://doi.org/10.1002/cbdv.202100261

Gajić M, Ilić BS, Bondžić B, Džambaski Z, Kojić VV, Jakimov DS, Kocić G, Šmelcerović A. 1,2,3,4-Tetrahydroisoquinoline Derivatives as a Novel Deoxyribonuclease I Inhibitors. in Chemistry and Biodisversity. 2021;18(8):e2100261.
doi:10.1002/cbdv.202100261 .

Gajić, Mihajlo, Ilić, Budimir S., Bondžić, Bojan, Džambaski, Zdravko, Kojić, Vesna V., Jakimov, Dimitar S., Kocić, Gordana, Šmelcerović, Andrija, "1,2,3,4-Tetrahydroisoquinoline Derivatives as a Novel Deoxyribonuclease I Inhibitors" in Chemistry and Biodisversity, 18, no. 8 (2021):e2100261,
https://doi.org/10.1002/cbdv.202100261 . .

TY  - CONF
AU  - Srećo Zelenović, Bojana
AU  - Kekezović, Slađana
AU  - Kojić, Vesna V.
AU  - Benedeković, Goran
AU  - Jadranin, Milka
AU  - Popsavin, Mirjana
AU  - Popsavin, Velimir
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7275
AB  - (-)-Goniofufurone (1) is a synthetic styryl lactone that exhibits significant antitumor activity. In the search for new and more potent antitumor agents the synthesis of lactones 5 and 6 was planned from D-glucose. Compounds 5 and 6 are designed as dephenylated analogues of 1 (Figure 1). The results of the evaluation of antiproliferative activity of 5 and 6 against a number of human tumor cell lines, as well as the structure-activity relationship (SAR), will be presented and discussed in details.
PB  - Valahia University of Targoviste
PB  - University Politehnica of Bucharest
C3  - Book of Abstracts - 9th International Conferences of the Chemical Societies of the South-Eastern European Countries, ICOSECS9, "Chemistry a Nature Challenger", Targoviste, Romania
T1  - Synthesis and antitumour activity of two dephenilated (-)-goniofufurone analogues
SP  - S3_P16
EP  - S3_P16
UR  - https://hdl.handle.net/21.15107/rcub_cer_7275
ER  - 

@conference{
author = "Srećo Zelenović, Bojana and Kekezović, Slađana and Kojić, Vesna V. and Benedeković, Goran and Jadranin, Milka and Popsavin, Mirjana and Popsavin, Velimir",
year = "2019",
abstract = "(-)-Goniofufurone (1) is a synthetic styryl lactone that exhibits significant antitumor activity. In the search for new and more potent antitumor agents the synthesis of lactones 5 and 6 was planned from D-glucose. Compounds 5 and 6 are designed as dephenylated analogues of 1 (Figure 1). The results of the evaluation of antiproliferative activity of 5 and 6 against a number of human tumor cell lines, as well as the structure-activity relationship (SAR), will be presented and discussed in details.",
publisher = "Valahia University of Targoviste, University Politehnica of Bucharest",
journal = "Book of Abstracts - 9th International Conferences of the Chemical Societies of the South-Eastern European Countries, ICOSECS9, "Chemistry a Nature Challenger", Targoviste, Romania",
title = "Synthesis and antitumour activity of two dephenilated (-)-goniofufurone analogues",
pages = "S3_P16-S3_P16",
url = "https://hdl.handle.net/21.15107/rcub_cer_7275"
}

Srećo Zelenović, B., Kekezović, S., Kojić, V. V., Benedeković, G., Jadranin, M., Popsavin, M.,& Popsavin, V.. (2019). Synthesis and antitumour activity of two dephenilated (-)-goniofufurone analogues. in Book of Abstracts - 9th International Conferences of the Chemical Societies of the South-Eastern European Countries, ICOSECS9, "Chemistry a Nature Challenger", Targoviste, Romania
Valahia University of Targoviste., S3_P16-S3_P16.
https://hdl.handle.net/21.15107/rcub_cer_7275

Srećo Zelenović B, Kekezović S, Kojić VV, Benedeković G, Jadranin M, Popsavin M, Popsavin V. Synthesis and antitumour activity of two dephenilated (-)-goniofufurone analogues. in Book of Abstracts - 9th International Conferences of the Chemical Societies of the South-Eastern European Countries, ICOSECS9, "Chemistry a Nature Challenger", Targoviste, Romania. 2019;:S3_P16-S3_P16.
https://hdl.handle.net/21.15107/rcub_cer_7275 .

Srećo Zelenović, Bojana, Kekezović, Slađana, Kojić, Vesna V., Benedeković, Goran, Jadranin, Milka, Popsavin, Mirjana, Popsavin, Velimir, "Synthesis and antitumour activity of two dephenilated (-)-goniofufurone analogues" in Book of Abstracts - 9th International Conferences of the Chemical Societies of the South-Eastern European Countries, ICOSECS9, "Chemistry a Nature Challenger", Targoviste, Romania (2019):S3_P16-S3_P16,
https://hdl.handle.net/21.15107/rcub_cer_7275 .

TY  - CONF
AU  - Popsavin, Mirjana
AU  - Kovačević, Ivana
AU  - Kekezović, Slađana
AU  - Svirčev, Miloš
AU  - Srećo Zelenović, Bojana
AU  - Kojić, Vesna V.
AU  - Jadranin, Milka
AU  - Popsavin, Velimir
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7095
AB  - Ostvarena je višefazna sinteza novih mimetika (+)-goniofufurona (1) sa tiofenskim prstenom umesto fenil grupe u položaju C-7 polazeći iz D-glukoze (Shema 1). Ispitana je in vitro citotoksična aktivnost novosintetizovanih mimetika prema odabranim tumorskim ćelijskim linijama, kao i prema jednoj normalnoj ćelijskoj liniji (fetalni fibroblasti pluća, MRC-5).
AB  - Multiphase synthesis of (+)-goniofufurone (1) mimetics with thiofene ring instead of phenyl group at the C-7 position is completed using D-glucose as a starting compound (Scheme 1). In vitro cytotoxicity of newly synthetized analogues against eleven human tumour cell lines and against a single normal cell line (MRC-5) was evaluated.
PB  - Belgrade : Serbian Chemical Society
C3  - Kratki izvodi radova - 55. Savetovanje Srpskog hemijskog društva, 8. i 9. juni 2018, Novi Sad / Book of abstracts - 55 Meeting of the Serbian Chemical Society, June 8-9, 2018, Novi Sad
T1  - Sinteza i in vitro antitumourska aktivnost novih mimetika goniofufurona sa tiofenskim prstenom na položaju C-7
T1  - Synthesis and in vitro antitumour activity of new goniofufurone mimics with  thiophene ring at the C-7 position
SP  - 82
EP  - 82
UR  - https://hdl.handle.net/21.15107/rcub_cer_7095
ER  - 

@conference{
author = "Popsavin, Mirjana and Kovačević, Ivana and Kekezović, Slađana and Svirčev, Miloš and Srećo Zelenović, Bojana and Kojić, Vesna V. and Jadranin, Milka and Popsavin, Velimir",
year = "2018",
abstract = "Ostvarena je višefazna sinteza novih mimetika (+)-goniofufurona (1) sa tiofenskim prstenom umesto fenil grupe u položaju C-7 polazeći iz D-glukoze (Shema 1). Ispitana je in vitro citotoksična aktivnost novosintetizovanih mimetika prema odabranim tumorskim ćelijskim linijama, kao i prema jednoj normalnoj ćelijskoj liniji (fetalni fibroblasti pluća, MRC-5)., Multiphase synthesis of (+)-goniofufurone (1) mimetics with thiofene ring instead of phenyl group at the C-7 position is completed using D-glucose as a starting compound (Scheme 1). In vitro cytotoxicity of newly synthetized analogues against eleven human tumour cell lines and against a single normal cell line (MRC-5) was evaluated.",
publisher = "Belgrade : Serbian Chemical Society",
journal = "Kratki izvodi radova - 55. Savetovanje Srpskog hemijskog društva, 8. i 9. juni 2018, Novi Sad / Book of abstracts - 55 Meeting of the Serbian Chemical Society, June 8-9, 2018, Novi Sad",
title = "Sinteza i in vitro antitumourska aktivnost novih mimetika goniofufurona sa tiofenskim prstenom na položaju C-7, Synthesis and in vitro antitumour activity of new goniofufurone mimics with  thiophene ring at the C-7 position",
pages = "82-82",
url = "https://hdl.handle.net/21.15107/rcub_cer_7095"
}

Popsavin, M., Kovačević, I., Kekezović, S., Svirčev, M., Srećo Zelenović, B., Kojić, V. V., Jadranin, M.,& Popsavin, V.. (2018). Sinteza i in vitro antitumourska aktivnost novih mimetika goniofufurona sa tiofenskim prstenom na položaju C-7. in Kratki izvodi radova - 55. Savetovanje Srpskog hemijskog društva, 8. i 9. juni 2018, Novi Sad / Book of abstracts - 55 Meeting of the Serbian Chemical Society, June 8-9, 2018, Novi Sad
Belgrade : Serbian Chemical Society., 82-82.
https://hdl.handle.net/21.15107/rcub_cer_7095

Popsavin M, Kovačević I, Kekezović S, Svirčev M, Srećo Zelenović B, Kojić VV, Jadranin M, Popsavin V. Sinteza i in vitro antitumourska aktivnost novih mimetika goniofufurona sa tiofenskim prstenom na položaju C-7. in Kratki izvodi radova - 55. Savetovanje Srpskog hemijskog društva, 8. i 9. juni 2018, Novi Sad / Book of abstracts - 55 Meeting of the Serbian Chemical Society, June 8-9, 2018, Novi Sad. 2018;:82-82.
https://hdl.handle.net/21.15107/rcub_cer_7095 .

Popsavin, Mirjana, Kovačević, Ivana, Kekezović, Slađana, Svirčev, Miloš, Srećo Zelenović, Bojana, Kojić, Vesna V., Jadranin, Milka, Popsavin, Velimir, "Sinteza i in vitro antitumourska aktivnost novih mimetika goniofufurona sa tiofenskim prstenom na položaju C-7" in Kratki izvodi radova - 55. Savetovanje Srpskog hemijskog društva, 8. i 9. juni 2018, Novi Sad / Book of abstracts - 55 Meeting of the Serbian Chemical Society, June 8-9, 2018, Novi Sad (2018):82-82,
https://hdl.handle.net/21.15107/rcub_cer_7095 .

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Sakač, Marija
AU  - Kuzminac, Ivana
AU  - Kojić, Vesna V.
AU  - Marković, Smilja B.
AU  - Vasiljević-Radović, Dana
AU  - Wu, Victoria
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2018
UR  - http://dais.sanu.ac.rs/123456789/4066
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3146
AB  - Low targeting efficiency and fast metabolism of antineoplastic drugs are hindrances to effective chemotherapies and there is an ongoing search for better drugs, but also better carriers. Steroid derivatives, 3β-hydroxy-16-hydroxymino-androst-5-en-17-one (A) and 3β,17β-dihydroxy-16-hydroxymino-androst-5-ene (B) as cancer growth inhibitors were chemically synthesized and captured in a carrier composed of hydroxyapatite (HAp) nanoparticles coated with chitosan oligosaccharide lactate (ChOLS). The only difference between the two derivatives is that A has a carbonyl group at the C17 position of the five-membered ring and B has a hydroxyl. This small difference in the structure resulted not only in different physicochemical properties of the A- and B-loaded HAp/ChOSL, but also in different biological activities. The morphology of drug-loaded HAp/ChOSL particles was spherical, but the size depended on the drug identity: d50 = 138 nm for A-loaded HAp/ChOSL and d50 = 223 nm for B-loaded HAp/ChOSL. Cell-selective toxicity was tested against human breast carcinoma (MCF7 and MDA-MB-231), human lung carcinoma (A549) and human lung fibroblasts (MRC-5). The small selectivity of pure derivatives A and B toward breast cancer cells became drastically increased when they were delivered using HAp/ChOSL particles. Whereas the ratio of the cytotoxicity imposed onto breast cancer cells and the cytotoxicity imposed onto healthy MRC-5 fibroblasts ranged from 1.5 to 1.7 for pure A and from 1.5 to 2.3 for pure derivative B depending on the concentration, it increased to 5.4 for A-loaded HAp/ChOSL and 5.1 for B-loaded HAp/ChOSL. FACS analysis demonstrated poor uptake of HAp/ChOSL particles by MCF7 cells, suggesting that the drug release occurs extracellularly. The augmented activity of the drugs was most likely due to sustained release, although the favorable positive charge of the carrier, allowing it to adhere to the negatively charged plasma membrane and release the drugs steadily and directly to the hydrophobic cell membrane milieu, was delineated as a possible complementary mechanism.
PB  - Royal Society of Chemistry
T2  - Journal of Materials Chemistry B
T1  - Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells
VL  - 6
SP  - 6957
EP  - 6968
DO  - 10.1039/C8TB01995A
ER  - 

@article{
author = "Ignjatović, Nenad and Sakač, Marija and Kuzminac, Ivana and Kojić, Vesna V. and Marković, Smilja B. and Vasiljević-Radović, Dana and Wu, Victoria and Uskoković, Vuk and Uskoković, Dragan",
year = "2018",
abstract = "Low targeting efficiency and fast metabolism of antineoplastic drugs are hindrances to effective chemotherapies and there is an ongoing search for better drugs, but also better carriers. Steroid derivatives, 3β-hydroxy-16-hydroxymino-androst-5-en-17-one (A) and 3β,17β-dihydroxy-16-hydroxymino-androst-5-ene (B) as cancer growth inhibitors were chemically synthesized and captured in a carrier composed of hydroxyapatite (HAp) nanoparticles coated with chitosan oligosaccharide lactate (ChOLS). The only difference between the two derivatives is that A has a carbonyl group at the C17 position of the five-membered ring and B has a hydroxyl. This small difference in the structure resulted not only in different physicochemical properties of the A- and B-loaded HAp/ChOSL, but also in different biological activities. The morphology of drug-loaded HAp/ChOSL particles was spherical, but the size depended on the drug identity: d50 = 138 nm for A-loaded HAp/ChOSL and d50 = 223 nm for B-loaded HAp/ChOSL. Cell-selective toxicity was tested against human breast carcinoma (MCF7 and MDA-MB-231), human lung carcinoma (A549) and human lung fibroblasts (MRC-5). The small selectivity of pure derivatives A and B toward breast cancer cells became drastically increased when they were delivered using HAp/ChOSL particles. Whereas the ratio of the cytotoxicity imposed onto breast cancer cells and the cytotoxicity imposed onto healthy MRC-5 fibroblasts ranged from 1.5 to 1.7 for pure A and from 1.5 to 2.3 for pure derivative B depending on the concentration, it increased to 5.4 for A-loaded HAp/ChOSL and 5.1 for B-loaded HAp/ChOSL. FACS analysis demonstrated poor uptake of HAp/ChOSL particles by MCF7 cells, suggesting that the drug release occurs extracellularly. The augmented activity of the drugs was most likely due to sustained release, although the favorable positive charge of the carrier, allowing it to adhere to the negatively charged plasma membrane and release the drugs steadily and directly to the hydrophobic cell membrane milieu, was delineated as a possible complementary mechanism.",
publisher = "Royal Society of Chemistry",
journal = "Journal of Materials Chemistry B",
title = "Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells",
volume = "6",
pages = "6957-6968",
doi = "10.1039/C8TB01995A"
}

Ignjatović, N., Sakač, M., Kuzminac, I., Kojić, V. V., Marković, S. B., Vasiljević-Radović, D., Wu, V., Uskoković, V.,& Uskoković, D.. (2018). Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells. in Journal of Materials Chemistry B
Royal Society of Chemistry., 6, 6957-6968.
https://doi.org/10.1039/C8TB01995A

Ignjatović N, Sakač M, Kuzminac I, Kojić VV, Marković SB, Vasiljević-Radović D, Wu V, Uskoković V, Uskoković D. Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells. in Journal of Materials Chemistry B. 2018;6:6957-6968.
doi:10.1039/C8TB01995A .

Ignjatović, Nenad, Sakač, Marija, Kuzminac, Ivana, Kojić, Vesna V., Marković, Smilja B., Vasiljević-Radović, Dana, Wu, Victoria, Uskoković, Vuk, Uskoković, Dragan, "Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells" in Journal of Materials Chemistry B, 6 (2018):6957-6968,
https://doi.org/10.1039/C8TB01995A . .

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Sakač, Marija
AU  - Kuzminac, Ivana
AU  - Kojić, Vesna V.
AU  - Marković, Smilja B.
AU  - Vasiljević-Radović, Dana
AU  - Wu, Victoria M.
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan P.
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2482
AB  - Low targeting efficiency and fast metabolism of antineoplastic drugs are hindrances to effective chemotherapies and there is an ongoing search for better drugs, but also better carriers. Steroid derivatives, 3-hydroxy-16-hydroxymino-androst-5-en-17-one (A) and 3,17-dihydroxy-16-hydroxymino-androst-5-ene (B) as cancer growth inhibitors were chemically synthesized and captured in a carrier composed of hydroxyapatite (HAp) nanoparticles coated with chitosan oligosaccharide lactate (ChOLS). The only difference between the two derivatives is that A has a carbonyl group at the C17 position of the five-membered ring and B has a hydroxyl. This small difference in the structure resulted not only in different physicochemical properties of the A- and B-loaded HAp/ChOSL, but also in different biological activities. The morphology of drug-loaded HAp/ChOSL particles was spherical, but the size depended on the drug identity: d(50) = 138 nm for A-loaded HAp/ChOSL and d(50) = 223 nm for B-loaded HAp/ChOSL. Cell-selective toxicity was tested against human breast carcinoma (MCF7 and MDA-MB-231), human lung carcinoma (A549) and human lung fibroblasts (MRC-5). The small selectivity of pure derivatives A and B toward breast cancer cells became drastically increased when they were delivered using HAp/ChOSL particles. Whereas the ratio of the cytotoxicity imposed onto breast cancer cells and the cytotoxicity imposed onto healthy MRC-5 fibroblasts ranged from 1.5 to 1.7 for pure A and from 1.5 to 2.3 for pure derivative B depending on the concentration, it increased to 5.4 for A-loaded HAp/ChOSL and 5.1 for B-loaded HAp/ChOSL. FACS analysis demonstrated poor uptake of HAp/ChOSL particles by MCF7 cells, suggesting that the drug release occurs extracellularly. The augmented activity of the drugs was most likely due to sustained release, although the favorable positive charge of the carrier, allowing it to adhere to the negatively charged plasma membrane and release the drugs steadily and directly to the hydrophobic cell membrane milieu, was delineated as a possible complementary mechanism.
PB  - Royal Society of Chemistry
T2  - Journal of Materials Chemistry B
T1  - Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells
VL  - 6
IS  - 43
SP  - 6957
EP  - 6968
DO  - 10.1039/c8tb01995a
ER  - 

@article{
author = "Ignjatović, Nenad and Sakač, Marija and Kuzminac, Ivana and Kojić, Vesna V. and Marković, Smilja B. and Vasiljević-Radović, Dana and Wu, Victoria M. and Uskoković, Vuk and Uskoković, Dragan P.",
year = "2018",
abstract = "Low targeting efficiency and fast metabolism of antineoplastic drugs are hindrances to effective chemotherapies and there is an ongoing search for better drugs, but also better carriers. Steroid derivatives, 3-hydroxy-16-hydroxymino-androst-5-en-17-one (A) and 3,17-dihydroxy-16-hydroxymino-androst-5-ene (B) as cancer growth inhibitors were chemically synthesized and captured in a carrier composed of hydroxyapatite (HAp) nanoparticles coated with chitosan oligosaccharide lactate (ChOLS). The only difference between the two derivatives is that A has a carbonyl group at the C17 position of the five-membered ring and B has a hydroxyl. This small difference in the structure resulted not only in different physicochemical properties of the A- and B-loaded HAp/ChOSL, but also in different biological activities. The morphology of drug-loaded HAp/ChOSL particles was spherical, but the size depended on the drug identity: d(50) = 138 nm for A-loaded HAp/ChOSL and d(50) = 223 nm for B-loaded HAp/ChOSL. Cell-selective toxicity was tested against human breast carcinoma (MCF7 and MDA-MB-231), human lung carcinoma (A549) and human lung fibroblasts (MRC-5). The small selectivity of pure derivatives A and B toward breast cancer cells became drastically increased when they were delivered using HAp/ChOSL particles. Whereas the ratio of the cytotoxicity imposed onto breast cancer cells and the cytotoxicity imposed onto healthy MRC-5 fibroblasts ranged from 1.5 to 1.7 for pure A and from 1.5 to 2.3 for pure derivative B depending on the concentration, it increased to 5.4 for A-loaded HAp/ChOSL and 5.1 for B-loaded HAp/ChOSL. FACS analysis demonstrated poor uptake of HAp/ChOSL particles by MCF7 cells, suggesting that the drug release occurs extracellularly. The augmented activity of the drugs was most likely due to sustained release, although the favorable positive charge of the carrier, allowing it to adhere to the negatively charged plasma membrane and release the drugs steadily and directly to the hydrophobic cell membrane milieu, was delineated as a possible complementary mechanism.",
publisher = "Royal Society of Chemistry",
journal = "Journal of Materials Chemistry B",
title = "Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells",
volume = "6",
number = "43",
pages = "6957-6968",
doi = "10.1039/c8tb01995a"
}

Ignjatović, N., Sakač, M., Kuzminac, I., Kojić, V. V., Marković, S. B., Vasiljević-Radović, D., Wu, V. M., Uskoković, V.,& Uskoković, D. P.. (2018). Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells. in Journal of Materials Chemistry B
Royal Society of Chemistry., 6(43), 6957-6968.
https://doi.org/10.1039/c8tb01995a

Ignjatović N, Sakač M, Kuzminac I, Kojić VV, Marković SB, Vasiljević-Radović D, Wu VM, Uskoković V, Uskoković DP. Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells. in Journal of Materials Chemistry B. 2018;6(43):6957-6968.
doi:10.1039/c8tb01995a .

Ignjatović, Nenad, Sakač, Marija, Kuzminac, Ivana, Kojić, Vesna V., Marković, Smilja B., Vasiljević-Radović, Dana, Wu, Victoria M., Uskoković, Vuk, Uskoković, Dragan P., "Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells" in Journal of Materials Chemistry B, 6, no. 43 (2018):6957-6968,
https://doi.org/10.1039/c8tb01995a . .

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Penov-Gasi, Katarina M.
AU  - Wu, Victoria M.
AU  - Ajduković, Jovana J.
AU  - Kojić, Vesna V.
AU  - Vasiljević-Radović, Dana
AU  - Kuzmanovic, Maja
AU  - Uskokovicć, Vuk
AU  - Uskoković, Dragan P.
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1996
AB  - In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(D,L)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17 beta-hydroxy-17 alpha-picolyl-androst-5-en-3 beta-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. H-1 NMR and C-13 NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the thermal degradation products and properties of A-loaded HAp/Ch-PLGA. The loading efficiency, as indicated by the comparison of enthalpies of phase transitions in pure A and A-loaded HAp/Ch-PLGA, equaled 7.47 wt.%. The release of A from HAp/Ch-PLGA was sustained, neither exhibiting a burst release nor plateauing after three weeks. Atomic force microscopy and particle size distribution analyses were used to confirm that the particles were spherical with a uniform size distribution of d(50) = 168 nm. In vitro cytotoxicity testing of A-loaded HAp/Ch-PLGA using MTT and trypan blue dye exclusion assays demonstrated that the particles were cytotoxic to the A549 human lung carcinoma cell line (46 +/- 2%), while simultaneously preserving high viability (83 +/- 3%) of regular MRC5 human lung fibroblasts and causing no harm to primary mouse lung fibroblasts. In conclusion, composite A-loaded HAp/Ch-PLGA particles could be seen as promising drug delivery platforms for selective cancer therapies, targeting malignant cells for destruction, while having a significantly lesser cytotoxic effect on the healthy cells.
PB  - Elsevier
T2  - Colloids and Surfaces B-Biointerfaces
T1  - Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor
VL  - 148
SP  - 629
EP  - 639
DO  - 10.1016/j.colsurfb.2016.09.041
ER  - 

@article{
author = "Ignjatović, Nenad and Penov-Gasi, Katarina M. and Wu, Victoria M. and Ajduković, Jovana J. and Kojić, Vesna V. and Vasiljević-Radović, Dana and Kuzmanovic, Maja and Uskokovicć, Vuk and Uskoković, Dragan P.",
year = "2016",
abstract = "In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(D,L)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17 beta-hydroxy-17 alpha-picolyl-androst-5-en-3 beta-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. H-1 NMR and C-13 NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the thermal degradation products and properties of A-loaded HAp/Ch-PLGA. The loading efficiency, as indicated by the comparison of enthalpies of phase transitions in pure A and A-loaded HAp/Ch-PLGA, equaled 7.47 wt.%. The release of A from HAp/Ch-PLGA was sustained, neither exhibiting a burst release nor plateauing after three weeks. Atomic force microscopy and particle size distribution analyses were used to confirm that the particles were spherical with a uniform size distribution of d(50) = 168 nm. In vitro cytotoxicity testing of A-loaded HAp/Ch-PLGA using MTT and trypan blue dye exclusion assays demonstrated that the particles were cytotoxic to the A549 human lung carcinoma cell line (46 +/- 2%), while simultaneously preserving high viability (83 +/- 3%) of regular MRC5 human lung fibroblasts and causing no harm to primary mouse lung fibroblasts. In conclusion, composite A-loaded HAp/Ch-PLGA particles could be seen as promising drug delivery platforms for selective cancer therapies, targeting malignant cells for destruction, while having a significantly lesser cytotoxic effect on the healthy cells.",
publisher = "Elsevier",
journal = "Colloids and Surfaces B-Biointerfaces",
title = "Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor",
volume = "148",
pages = "629-639",
doi = "10.1016/j.colsurfb.2016.09.041"
}

Ignjatović, N., Penov-Gasi, K. M., Wu, V. M., Ajduković, J. J., Kojić, V. V., Vasiljević-Radović, D., Kuzmanovic, M., Uskokovicć, V.,& Uskoković, D. P.. (2016). Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor. in Colloids and Surfaces B-Biointerfaces
Elsevier., 148, 629-639.
https://doi.org/10.1016/j.colsurfb.2016.09.041

Ignjatović N, Penov-Gasi KM, Wu VM, Ajduković JJ, Kojić VV, Vasiljević-Radović D, Kuzmanovic M, Uskokovicć V, Uskoković DP. Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor. in Colloids and Surfaces B-Biointerfaces. 2016;148:629-639.
doi:10.1016/j.colsurfb.2016.09.041 .

Ignjatović, Nenad, Penov-Gasi, Katarina M., Wu, Victoria M., Ajduković, Jovana J., Kojić, Vesna V., Vasiljević-Radović, Dana, Kuzmanovic, Maja, Uskokovicć, Vuk, Uskoković, Dragan P., "Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor" in Colloids and Surfaces B-Biointerfaces, 148 (2016):629-639,
https://doi.org/10.1016/j.colsurfb.2016.09.041 . .

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Penov Gaši, Katarina
AU  - Wu, Victoria
AU  - Ajduković, Jovana
AU  - Kojić, Vesna V.
AU  - Vasiljević-Radović, Dana
AU  - Kuzmanović, Maja
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan P.
PY  - 2016
UR  - http://dais.sanu.ac.rs/123456789/15984
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2644
AB  - In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. 1H NMR and 13C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the thermal degradation products and properties of A-loaded HAp/Ch-PLGA. The loading efficiency, as indicated by the comparison of enthalpies of phase transitions in pure A and A-loaded HAp/Ch-PLGA, equaled 7.47 wt.%. The release of A from HAp/Ch-PLGA was sustained, neither exhibiting a burst release nor plateauing after three weeks. Atomic force microscopy and particle size distribution analyses were used to confirm that the particles were spherical with a uniform size distribution of d50 = 168 nm. In vitro cytotoxicity testing of A-loaded HAp/Ch-PLGA using MTT and trypan blue dye exclusion assays demonstrated that the particles were cytotoxic to the A549 human lung carcinoma cell line (46 ± 2%), while simultaneously preserving high viability (83 ± 3%) of regular MRC5 human lung fibroblasts and causing no harm to primary mouse lung fibroblasts. In conclusion, composite A-loaded HAp/Ch-PLGA particles could be seen as promising drug delivery platforms for selective cancer therapies, targeting malignant cells for destruction, while having a significantly lesser cytotoxic effect on the healthy cells.
T2  - Colloids and Surfaces B: Biointerfaces
T1  - Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor
VL  - 148
SP  - 629
EP  - 639
DO  - 10.1016/j.colsurfb.2016.09.041
ER  - 

@article{
author = "Ignjatović, Nenad and Penov Gaši, Katarina and Wu, Victoria and Ajduković, Jovana and Kojić, Vesna V. and Vasiljević-Radović, Dana and Kuzmanović, Maja and Uskoković, Vuk and Uskoković, Dragan P.",
year = "2016",
abstract = "In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. 1H NMR and 13C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the thermal degradation products and properties of A-loaded HAp/Ch-PLGA. The loading efficiency, as indicated by the comparison of enthalpies of phase transitions in pure A and A-loaded HAp/Ch-PLGA, equaled 7.47 wt.%. The release of A from HAp/Ch-PLGA was sustained, neither exhibiting a burst release nor plateauing after three weeks. Atomic force microscopy and particle size distribution analyses were used to confirm that the particles were spherical with a uniform size distribution of d50 = 168 nm. In vitro cytotoxicity testing of A-loaded HAp/Ch-PLGA using MTT and trypan blue dye exclusion assays demonstrated that the particles were cytotoxic to the A549 human lung carcinoma cell line (46 ± 2%), while simultaneously preserving high viability (83 ± 3%) of regular MRC5 human lung fibroblasts and causing no harm to primary mouse lung fibroblasts. In conclusion, composite A-loaded HAp/Ch-PLGA particles could be seen as promising drug delivery platforms for selective cancer therapies, targeting malignant cells for destruction, while having a significantly lesser cytotoxic effect on the healthy cells.",
journal = "Colloids and Surfaces B: Biointerfaces",
title = "Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor",
volume = "148",
pages = "629-639",
doi = "10.1016/j.colsurfb.2016.09.041"
}

Ignjatović, N., Penov Gaši, K., Wu, V., Ajduković, J., Kojić, V. V., Vasiljević-Radović, D., Kuzmanović, M., Uskoković, V.,& Uskoković, D. P.. (2016). Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor. in Colloids and Surfaces B: Biointerfaces, 148, 629-639.
https://doi.org/10.1016/j.colsurfb.2016.09.041

Ignjatović N, Penov Gaši K, Wu V, Ajduković J, Kojić VV, Vasiljević-Radović D, Kuzmanović M, Uskoković V, Uskoković DP. Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor. in Colloids and Surfaces B: Biointerfaces. 2016;148:629-639.
doi:10.1016/j.colsurfb.2016.09.041 .

Ignjatović, Nenad, Penov Gaši, Katarina, Wu, Victoria, Ajduković, Jovana, Kojić, Vesna V., Vasiljević-Radović, Dana, Kuzmanović, Maja, Uskoković, Vuk, Uskoković, Dragan P., "Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor" in Colloids and Surfaces B: Biointerfaces, 148 (2016):629-639,
https://doi.org/10.1016/j.colsurfb.2016.09.041 . .

TY  - CONF
AU  - Ignjatović, Nenad
AU  - Penov Gaši, Katarina
AU  - Wu, Victoria
AU  - Ajduković, Jovana
AU  - Kojić, Vesna V.
AU  - Vasiljević-Radović, Dana
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2016
UR  - http://dais.sanu.ac.rs/123456789/896
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2864
AB  - The applicative potential of synthetic calcium phosphates, especially hydroxyapatite (HAp), has become intensely broadened in the past 10 years, from bone tissue engineering to multiple other fields of biomedicine. Previously we have shown that hydroxyapatite nanoparticles coated with chitosan-poly(D,L)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous administration into mice. For this purpose radioactive 125-Iodine (125I), a low energy gamma emitter, was used to develop a novel in situ method for radiolabeling of particles and investigation of their biodistribution. In this study we utilize an emulsification process and freeze drying to load the composite particles based on hydroxyapatite nanocarrier, chitosane and poly(lactic-co-glycolic acid) with 17β- hydroxy-17α-picolyl-androst-5-en-3β-acetate (A), a chemotherapeutic derivative of androstane. The picolyl androstane derivatives showed high potency in the cell inhibitors of hormonedependent cancers (adenocarcinoma, prostate cancer, cervix carcinoma, colon cancer, etc.). 1H NMR, 13C NMR and high-resolution time-of-flight mass spectrometry (MS) techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The synthesized particles of A-loaded HAp/Ch-PLGA were found to be spherical in shape with a uniform size distribution of d50=168 nm. The release of A from HAp/Ch-PLGA was sustained, with no burst release or plateauing after three weeks. The obtained results of the DET and MTT tests show that the particles of A-loaded HAp/Ch-PLGA exhibit almost three times higher cytotoxicity towards lung adenocarcinoma cells (A549) than towards healthy cells (MRC5), while at the same time allowing twice as fast recovery of healthy cells. We have also analyzed the period of recovery of healthy, as well as cancer cells, following the treatment with A-loaded HAp/Ch-PLGA. After treatment with A-loaded HAp/Ch-PLGA, healthy cells recover twice as fast as the malignant ones. Immunofluorescent staining of primary fibroblasts interacting with HAp/Ch-PLGA and A-HAp/Ch-PLGA particles demonstrates no negative morphological or proliferative effects on cells.
PB  - Belgrade : Materials Research Society of Serbia
C3  - Programme and The Book of Abstracts / Eighteenth Annual Conference YUCOMAT 2016, Herceg Novi, September 5-10, 2016
T1  - Tumor-selective hybrid system based on hydroxyapatite nanocarrier, chitosan, poly(lactic-co-glycolic acid) and androstan derivate
SP  - 27
EP  - 27
UR  - https://hdl.handle.net/21.15107/rcub_dais_896
ER  - 

@conference{
author = "Ignjatović, Nenad and Penov Gaši, Katarina and Wu, Victoria and Ajduković, Jovana and Kojić, Vesna V. and Vasiljević-Radović, Dana and Uskoković, Vuk and Uskoković, Dragan",
year = "2016",
abstract = "The applicative potential of synthetic calcium phosphates, especially hydroxyapatite (HAp), has become intensely broadened in the past 10 years, from bone tissue engineering to multiple other fields of biomedicine. Previously we have shown that hydroxyapatite nanoparticles coated with chitosan-poly(D,L)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous administration into mice. For this purpose radioactive 125-Iodine (125I), a low energy gamma emitter, was used to develop a novel in situ method for radiolabeling of particles and investigation of their biodistribution. In this study we utilize an emulsification process and freeze drying to load the composite particles based on hydroxyapatite nanocarrier, chitosane and poly(lactic-co-glycolic acid) with 17β- hydroxy-17α-picolyl-androst-5-en-3β-acetate (A), a chemotherapeutic derivative of androstane. The picolyl androstane derivatives showed high potency in the cell inhibitors of hormonedependent cancers (adenocarcinoma, prostate cancer, cervix carcinoma, colon cancer, etc.). 1H NMR, 13C NMR and high-resolution time-of-flight mass spectrometry (MS) techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The synthesized particles of A-loaded HAp/Ch-PLGA were found to be spherical in shape with a uniform size distribution of d50=168 nm. The release of A from HAp/Ch-PLGA was sustained, with no burst release or plateauing after three weeks. The obtained results of the DET and MTT tests show that the particles of A-loaded HAp/Ch-PLGA exhibit almost three times higher cytotoxicity towards lung adenocarcinoma cells (A549) than towards healthy cells (MRC5), while at the same time allowing twice as fast recovery of healthy cells. We have also analyzed the period of recovery of healthy, as well as cancer cells, following the treatment with A-loaded HAp/Ch-PLGA. After treatment with A-loaded HAp/Ch-PLGA, healthy cells recover twice as fast as the malignant ones. Immunofluorescent staining of primary fibroblasts interacting with HAp/Ch-PLGA and A-HAp/Ch-PLGA particles demonstrates no negative morphological or proliferative effects on cells.",
publisher = "Belgrade : Materials Research Society of Serbia",
journal = "Programme and The Book of Abstracts / Eighteenth Annual Conference YUCOMAT 2016, Herceg Novi, September 5-10, 2016",
title = "Tumor-selective hybrid system based on hydroxyapatite nanocarrier, chitosan, poly(lactic-co-glycolic acid) and androstan derivate",
pages = "27-27",
url = "https://hdl.handle.net/21.15107/rcub_dais_896"
}

Ignjatović, N., Penov Gaši, K., Wu, V., Ajduković, J., Kojić, V. V., Vasiljević-Radović, D., Uskoković, V.,& Uskoković, D.. (2016). Tumor-selective hybrid system based on hydroxyapatite nanocarrier, chitosan, poly(lactic-co-glycolic acid) and androstan derivate. in Programme and The Book of Abstracts / Eighteenth Annual Conference YUCOMAT 2016, Herceg Novi, September 5-10, 2016
Belgrade : Materials Research Society of Serbia., 27-27.
https://hdl.handle.net/21.15107/rcub_dais_896

Ignjatović N, Penov Gaši K, Wu V, Ajduković J, Kojić VV, Vasiljević-Radović D, Uskoković V, Uskoković D. Tumor-selective hybrid system based on hydroxyapatite nanocarrier, chitosan, poly(lactic-co-glycolic acid) and androstan derivate. in Programme and The Book of Abstracts / Eighteenth Annual Conference YUCOMAT 2016, Herceg Novi, September 5-10, 2016. 2016;:27-27.
https://hdl.handle.net/21.15107/rcub_dais_896 .

Ignjatović, Nenad, Penov Gaši, Katarina, Wu, Victoria, Ajduković, Jovana, Kojić, Vesna V., Vasiljević-Radović, Dana, Uskoković, Vuk, Uskoković, Dragan, "Tumor-selective hybrid system based on hydroxyapatite nanocarrier, chitosan, poly(lactic-co-glycolic acid) and androstan derivate" in Programme and The Book of Abstracts / Eighteenth Annual Conference YUCOMAT 2016, Herceg Novi, September 5-10, 2016 (2016):27-27,
https://hdl.handle.net/21.15107/rcub_dais_896 .

TY  - CONF
AU  - Svirčev, Miloš
AU  - Popsavin, Mirjana
AU  - Kovačević, Ivana
AU  - Kojić, Vesna V.
AU  - Bogdanović, Gordana
AU  - Jadranin, Milka
AU  - Popsavin, Velimir
PY  - 2012
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7276
AB  - Herein we report a total synthesis of two novel goniofufurone and 7-epi-goniofufurone isosteres bearing a 2-thiazolyl-4-amide moiety instead of the phenyl group at C-7, as well as O-benzyl instead of hydroxyl group at C-5.
PB  - Wiley
C3  - 22nd International Symposium on Medicinal Chemistry, ISMC 2012, Berlin, Germany
T1  - Synthesis and Biological Activity of new 5-O-Benzyl-7-thiazolyl Isosteres of goniofufurone and 7-epi-goniofufurone
SP  - 342
EP  - 342
UR  - https://hdl.handle.net/21.15107/rcub_cer_7276
ER  - 

@conference{
author = "Svirčev, Miloš and Popsavin, Mirjana and Kovačević, Ivana and Kojić, Vesna V. and Bogdanović, Gordana and Jadranin, Milka and Popsavin, Velimir",
year = "2012",
abstract = "Herein we report a total synthesis of two novel goniofufurone and 7-epi-goniofufurone isosteres bearing a 2-thiazolyl-4-amide moiety instead of the phenyl group at C-7, as well as O-benzyl instead of hydroxyl group at C-5.",
publisher = "Wiley",
journal = "22nd International Symposium on Medicinal Chemistry, ISMC 2012, Berlin, Germany",
title = "Synthesis and Biological Activity of new 5-O-Benzyl-7-thiazolyl Isosteres of goniofufurone and 7-epi-goniofufurone",
pages = "342-342",
url = "https://hdl.handle.net/21.15107/rcub_cer_7276"
}

Svirčev, M., Popsavin, M., Kovačević, I., Kojić, V. V., Bogdanović, G., Jadranin, M.,& Popsavin, V.. (2012). Synthesis and Biological Activity of new 5-O-Benzyl-7-thiazolyl Isosteres of goniofufurone and 7-epi-goniofufurone. in 22nd International Symposium on Medicinal Chemistry, ISMC 2012, Berlin, Germany
Wiley., 342-342.
https://hdl.handle.net/21.15107/rcub_cer_7276

Svirčev M, Popsavin M, Kovačević I, Kojić VV, Bogdanović G, Jadranin M, Popsavin V. Synthesis and Biological Activity of new 5-O-Benzyl-7-thiazolyl Isosteres of goniofufurone and 7-epi-goniofufurone. in 22nd International Symposium on Medicinal Chemistry, ISMC 2012, Berlin, Germany. 2012;:342-342.
https://hdl.handle.net/21.15107/rcub_cer_7276 .

Svirčev, Miloš, Popsavin, Mirjana, Kovačević, Ivana, Kojić, Vesna V., Bogdanović, Gordana, Jadranin, Milka, Popsavin, Velimir, "Synthesis and Biological Activity of new 5-O-Benzyl-7-thiazolyl Isosteres of goniofufurone and 7-epi-goniofufurone" in 22nd International Symposium on Medicinal Chemistry, ISMC 2012, Berlin, Germany (2012):342-342,
https://hdl.handle.net/21.15107/rcub_cer_7276 .

TY  - CONF
AU  - Srećo, Bojana
AU  - Benedeković, Goran
AU  - Popsavin, Mirjana
AU  - Kojić, Vesna V.
AU  - Bogdanović, Gordana
AU  - Jadranin, Milka
AU  - Popsavin, Velimir
PY  - 2010
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7273
AB  - Herein we describe a modified total synthesis of (+)-Muricatacin starting from D-xylose, as well as synthesis of two new conformationally constrained (+)-muricatacin mimics from D-glucose.
PB  - IUPAC
C3  - The 18th International Conference on Organic Synthesis, IUPAC ICOS-18, August 1-6 2010, Bergen, Norway
T1  - Synthesis and antiprol iferative activity of (+)-muricatacin and two novel conformationally constrained analogues
SP  - 147
EP  - 147
UR  - https://hdl.handle.net/21.15107/rcub_cer_7273
ER  - 

@conference{
author = "Srećo, Bojana and Benedeković, Goran and Popsavin, Mirjana and Kojić, Vesna V. and Bogdanović, Gordana and Jadranin, Milka and Popsavin, Velimir",
year = "2010",
abstract = "Herein we describe a modified total synthesis of (+)-Muricatacin starting from D-xylose, as well as synthesis of two new conformationally constrained (+)-muricatacin mimics from D-glucose.",
publisher = "IUPAC",
journal = "The 18th International Conference on Organic Synthesis, IUPAC ICOS-18, August 1-6 2010, Bergen, Norway",
title = "Synthesis and antiprol iferative activity of (+)-muricatacin and two novel conformationally constrained analogues",
pages = "147-147",
url = "https://hdl.handle.net/21.15107/rcub_cer_7273"
}

Srećo, B., Benedeković, G., Popsavin, M., Kojić, V. V., Bogdanović, G., Jadranin, M.,& Popsavin, V.. (2010). Synthesis and antiprol iferative activity of (+)-muricatacin and two novel conformationally constrained analogues. in The 18th International Conference on Organic Synthesis, IUPAC ICOS-18, August 1-6 2010, Bergen, Norway
IUPAC., 147-147.
https://hdl.handle.net/21.15107/rcub_cer_7273

Srećo B, Benedeković G, Popsavin M, Kojić VV, Bogdanović G, Jadranin M, Popsavin V. Synthesis and antiprol iferative activity of (+)-muricatacin and two novel conformationally constrained analogues. in The 18th International Conference on Organic Synthesis, IUPAC ICOS-18, August 1-6 2010, Bergen, Norway. 2010;:147-147.
https://hdl.handle.net/21.15107/rcub_cer_7273 .

Srećo, Bojana, Benedeković, Goran, Popsavin, Mirjana, Kojić, Vesna V., Bogdanović, Gordana, Jadranin, Milka, Popsavin, Velimir, "Synthesis and antiprol iferative activity of (+)-muricatacin and two novel conformationally constrained analogues" in The 18th International Conference on Organic Synthesis, IUPAC ICOS-18, August 1-6 2010, Bergen, Norway (2010):147-147,
https://hdl.handle.net/21.15107/rcub_cer_7273 .

TY  - CONF
AU  - Svirčev, Miloš
AU  - Popsavin, Mirjana
AU  - Kojić, Vesna V.
AU  - Bogdanović, Gordana
AU  - Jadranin, Milka
AU  - Popsavin, Velimir
PY  - 2010
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7274
AB  - Herein we report a total synthesis of two novel (7-epi-)goniofufurone isosteres bearing a 2-thiazolyl-4-carboxylic acid ethyl ester moiety instead of the aromatic ring at C-7.
PB  - IUPAC
C3  - The 18th International Conference on Organic Synthesis, IUPAC ICOS-18, August 1-6 2010, Bergen, Norway
T1  - Synthesis and biological activity of new thiazole isosteres of goniofufurone and 7-epi-goniofufurone
SP  - 431
EP  - 431
UR  - https://hdl.handle.net/21.15107/rcub_cer_7274
ER  - 

@conference{
author = "Svirčev, Miloš and Popsavin, Mirjana and Kojić, Vesna V. and Bogdanović, Gordana and Jadranin, Milka and Popsavin, Velimir",
year = "2010",
abstract = "Herein we report a total synthesis of two novel (7-epi-)goniofufurone isosteres bearing a 2-thiazolyl-4-carboxylic acid ethyl ester moiety instead of the aromatic ring at C-7.",
publisher = "IUPAC",
journal = "The 18th International Conference on Organic Synthesis, IUPAC ICOS-18, August 1-6 2010, Bergen, Norway",
title = "Synthesis and biological activity of new thiazole isosteres of goniofufurone and 7-epi-goniofufurone",
pages = "431-431",
url = "https://hdl.handle.net/21.15107/rcub_cer_7274"
}

Svirčev, M., Popsavin, M., Kojić, V. V., Bogdanović, G., Jadranin, M.,& Popsavin, V.. (2010). Synthesis and biological activity of new thiazole isosteres of goniofufurone and 7-epi-goniofufurone. in The 18th International Conference on Organic Synthesis, IUPAC ICOS-18, August 1-6 2010, Bergen, Norway
IUPAC., 431-431.
https://hdl.handle.net/21.15107/rcub_cer_7274

Svirčev M, Popsavin M, Kojić VV, Bogdanović G, Jadranin M, Popsavin V. Synthesis and biological activity of new thiazole isosteres of goniofufurone and 7-epi-goniofufurone. in The 18th International Conference on Organic Synthesis, IUPAC ICOS-18, August 1-6 2010, Bergen, Norway. 2010;:431-431.
https://hdl.handle.net/21.15107/rcub_cer_7274 .

Svirčev, Miloš, Popsavin, Mirjana, Kojić, Vesna V., Bogdanović, Gordana, Jadranin, Milka, Popsavin, Velimir, "Synthesis and biological activity of new thiazole isosteres of goniofufurone and 7-epi-goniofufurone" in The 18th International Conference on Organic Synthesis, IUPAC ICOS-18, August 1-6 2010, Bergen, Norway (2010):431-431,
https://hdl.handle.net/21.15107/rcub_cer_7274 .