Chitosan nanobeads loaded with Biginelli hybrids as cell-selective toxicity systems with a homogeneous distribution of the cell cycle in cancer treatment
Authors
Ristovski (Trifunović), JovanaŽižak, Željko
Marković, Smilja

Janković, Nenad
Ignjatović, Nenad

Article (Published version)
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Show full item recordAbstract
Tetrahydropyrimidines are a class of azaheterocycles, also called Biginelli hybrids (obtained from the Biginelli reaction), that have attracted an enormous interest in the medicinal chemistry community in recent years, due to a broad biological activity, such as anticancer, antiviral, anti-inflammatory, antidiabetic, antituberculosis activities, etc. According to SciFinder®, more than 70 000 different Biginelli-like compounds have been covered in publications. However, although the Biginelli reaction can yield a large number of compounds with a broad range of activities, none of them have been captured in a carrier. In this study, chitosan-based (Ch) nanoparticles (NPs) containing three different molecules (Biginelli hybrids) were developed and tested for the first time as simple and promising vehicles for anticancer Biginelli-based drugs. The key features of NPs, such as size, surface morphology, drug encapsulation efficiency, and in vitro release were systematically investigated. Rat...her weak cell selectivity of pure Biginelli hybrids (A–C) to selected cancer cell lines has improved and this has been accompanied with two-to-four times stronger cytotoxic effect of A–C loaded Ch NPs, with a triple reduction in toxicity to healthy cells (MRC-5). It has been observed that the examined NPs induce apoptosis. The cell cycle analysis has confirmed the influence of A-loaded Ch (A-Ch), B-loaded Ch (B-Ch), and C-loaded Ch (C-Ch) on the cell cycle distribution, which was homogenously affected. This is the difference with regard to the effect of A, B, and C on the cell cycle. It has been established that the increased selectivity and antitumor activity of NPs are related to the presence of the carrier.
Keywords:
drug delivery / bioactivity / chitosan / Biginelli hybrids / toxicity / cancer treatmentSource:
RSC Advances, 2020, 10, 68, 41542-41550Publisher:
- Royal Society of Chemistry
Funding / projects:
- Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200175 (Institute of Technical Sciences of SASA, Belgrade) (RS-200175)
- Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200378 (Institute of Information Technology) (RS-200378)
Note:
- Supplementary material: https://hdl.handle.net/21.15107/rcub_dais_9815
Related info:
- Referenced by
https://hdl.handle.net/21.15107/rcub_dais_9815
DOI: 10.1039/D0RA08085C
ISSN: 2046-2069
WoS: 000591071500027
Scopus: 2-s2.0-85096522402
URI
https://pubs.rsc.org/en/content/articlelanding/2020/ra/d0ra08085chttps://dais.sanu.ac.rs/123456789/9814
Institution/Community
Институт техничких наука САНУ / Institute of Technical Sciences of SASATY - JOUR AU - Ristovski (Trifunović), Jovana AU - Žižak, Željko AU - Marković, Smilja AU - Janković, Nenad AU - Ignjatović, Nenad PY - 2020 UR - https://pubs.rsc.org/en/content/articlelanding/2020/ra/d0ra08085c UR - https://dais.sanu.ac.rs/123456789/9814 AB - Tetrahydropyrimidines are a class of azaheterocycles, also called Biginelli hybrids (obtained from the Biginelli reaction), that have attracted an enormous interest in the medicinal chemistry community in recent years, due to a broad biological activity, such as anticancer, antiviral, anti-inflammatory, antidiabetic, antituberculosis activities, etc. According to SciFinder®, more than 70 000 different Biginelli-like compounds have been covered in publications. However, although the Biginelli reaction can yield a large number of compounds with a broad range of activities, none of them have been captured in a carrier. In this study, chitosan-based (Ch) nanoparticles (NPs) containing three different molecules (Biginelli hybrids) were developed and tested for the first time as simple and promising vehicles for anticancer Biginelli-based drugs. The key features of NPs, such as size, surface morphology, drug encapsulation efficiency, and in vitro release were systematically investigated. Rather weak cell selectivity of pure Biginelli hybrids (A–C) to selected cancer cell lines has improved and this has been accompanied with two-to-four times stronger cytotoxic effect of A–C loaded Ch NPs, with a triple reduction in toxicity to healthy cells (MRC-5). It has been observed that the examined NPs induce apoptosis. The cell cycle analysis has confirmed the influence of A-loaded Ch (A-Ch), B-loaded Ch (B-Ch), and C-loaded Ch (C-Ch) on the cell cycle distribution, which was homogenously affected. This is the difference with regard to the effect of A, B, and C on the cell cycle. It has been established that the increased selectivity and antitumor activity of NPs are related to the presence of the carrier. PB - Royal Society of Chemistry T2 - RSC Advances T1 - Chitosan nanobeads loaded with Biginelli hybrids as cell-selective toxicity systems with a homogeneous distribution of the cell cycle in cancer treatment SP - 41542 EP - 41550 VL - 10 IS - 68 DO - 10.1039/D0RA08085C UR - https://hdl.handle.net/21.15107/rcub_dais_9814 ER -
@article{ author = "Ristovski (Trifunović), Jovana and Žižak, Željko and Marković, Smilja and Janković, Nenad and Ignjatović, Nenad", year = "2020", abstract = "Tetrahydropyrimidines are a class of azaheterocycles, also called Biginelli hybrids (obtained from the Biginelli reaction), that have attracted an enormous interest in the medicinal chemistry community in recent years, due to a broad biological activity, such as anticancer, antiviral, anti-inflammatory, antidiabetic, antituberculosis activities, etc. According to SciFinder®, more than 70 000 different Biginelli-like compounds have been covered in publications. However, although the Biginelli reaction can yield a large number of compounds with a broad range of activities, none of them have been captured in a carrier. In this study, chitosan-based (Ch) nanoparticles (NPs) containing three different molecules (Biginelli hybrids) were developed and tested for the first time as simple and promising vehicles for anticancer Biginelli-based drugs. The key features of NPs, such as size, surface morphology, drug encapsulation efficiency, and in vitro release were systematically investigated. Rather weak cell selectivity of pure Biginelli hybrids (A–C) to selected cancer cell lines has improved and this has been accompanied with two-to-four times stronger cytotoxic effect of A–C loaded Ch NPs, with a triple reduction in toxicity to healthy cells (MRC-5). It has been observed that the examined NPs induce apoptosis. The cell cycle analysis has confirmed the influence of A-loaded Ch (A-Ch), B-loaded Ch (B-Ch), and C-loaded Ch (C-Ch) on the cell cycle distribution, which was homogenously affected. This is the difference with regard to the effect of A, B, and C on the cell cycle. It has been established that the increased selectivity and antitumor activity of NPs are related to the presence of the carrier.", publisher = "Royal Society of Chemistry", journal = "RSC Advances", title = "Chitosan nanobeads loaded with Biginelli hybrids as cell-selective toxicity systems with a homogeneous distribution of the cell cycle in cancer treatment", pages = "41542-41550", volume = "10", number = "68", doi = "10.1039/D0RA08085C", url = "https://hdl.handle.net/21.15107/rcub_dais_9814" }
Ristovski (Trifunović), J., Žižak, Ž., Marković, S., Janković, N.,& Ignjatović, N.. (2020). Chitosan nanobeads loaded with Biginelli hybrids as cell-selective toxicity systems with a homogeneous distribution of the cell cycle in cancer treatment. in RSC Advances Royal Society of Chemistry., 10(68), 41542-41550. https://doi.org/10.1039/D0RA08085C https://hdl.handle.net/21.15107/rcub_dais_9814
Ristovski (Trifunović) J, Žižak Ž, Marković S, Janković N, Ignjatović N. Chitosan nanobeads loaded with Biginelli hybrids as cell-selective toxicity systems with a homogeneous distribution of the cell cycle in cancer treatment. in RSC Advances. 2020;10(68):41542-41550. doi:10.1039/D0RA08085C https://hdl.handle.net/21.15107/rcub_dais_9814 .
Ristovski (Trifunović), Jovana, Žižak, Željko, Marković, Smilja, Janković, Nenad, Ignjatović, Nenad, "Chitosan nanobeads loaded with Biginelli hybrids as cell-selective toxicity systems with a homogeneous distribution of the cell cycle in cancer treatment" in RSC Advances, 10, no. 68 (2020):41542-41550, https://doi.org/10.1039/D0RA08085C ., https://hdl.handle.net/21.15107/rcub_dais_9814 .