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http://hdl.handle.net/11320/16606
Tytuł: | Synergistic effect of folate-conjugated thermosensitive polymers and 5-fluorouracil in the treatment of colon cancer |
Autorzy: | Wilczewska, Agnieszka Z. Niemirowicz - Laskowska, Katarzyna Markiewicz, Karolina H. Misztalewska - Turkowicz, Iwona Dudź, Ewelina Milewska, Sylwia Misiak, Paweł Kurowska, Izabela Sadowska, Anna Car, Halina Siemiaszko, Gabriela |
Słowa kluczowe: | Folic acid Colon cancer 5-Fluorouracil Drug delivery system Targeted therapy RAFT/MADIX polymerization Polymeric micelles Thermoresponsive polymer |
Data wydania: | 2021 |
Data dodania: | 4-cze-2024 |
Wydawca: | BMC |
Źródło: | Cancer Nanotechnology, Volume 12 (2021), p. 1-24 |
Abstrakt: | Background: In recent years, targeted drug delivery strategies have received special attention from the scientifc world due to advantages such as more efective therapy and reduction of side efects. The principle of operation is delayed excretion from the bloodstream of the drug delivery system compared to the drug itself, as well as facilitated penetration into diseased cells thanks to the use of ligands recognized by appropriate receptors. Particularly interesting drug carriers are amphiphilic copolymers that form nano-sized micelles with a drug, which can release the drug at a specifc place in the body under the infuence of appropriate stimuli. Results: We describe the synthesis of the diblock polymer, poly(2-hydroxyethyl acrylate)-b-poly(N-vinylcaprolactam) using RAFT/MADIX (Reversible Addition-Fragmentation chain Transfer/MAcromolecular Design by Interchange of Xanthate) controlled polymerization afording polymers with good dispersity according to SEC (Size-Exclusion Chromatography). Some post-modifcations of the polymer with folic acid were then performed as evidenced by NMR (Nuclear Magnetic Resonance), UV–Vis (UltraViolet–Visible) and FT-IR (Fourier-Transform Infrared) spectroscopy, and TGA (ThermoGravimetricAnalysis). The formation of stable micellar systems from polymers with and without the drug, 5-fuorouracil, was confrmed by DLS (Dynamic Light Scattering) and zeta potential measurements, and TEM (Transmission Eelectron Microscopy) imaging. Finally, the cloud point of the polymers was investigated, which turned out to be close to the temperature of the human body. Most importantly, these micellar systems have been explored as a drug delivery system against colon cancer, showing increased cytotoxicity compared to the drug alone. This efect was achieved due to the easier cellular uptake by the interaction of folic acid and its receptors on the surface of cancer cells. Conclusions: The presented results constitute a solid foundation for the implementation of a nano-sized drug delivery system containing folic acid for practical use in the treatment of drug-resistant cancer, as well as more efective therapy with fewer side efects. |
Afiliacja: | Gabriela Siemiaszko - Faculty of Chemistry, University of Bialystok, Ciolkowskiego 1K, 15‑245 Bialystok, Poland Katarzyna Niemirowicz‑Laskowska - Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna 37, 15‑361 Bialystok, Poland Karolina H. Markiewicz - Faculty of Chemistry, University of Bialystok, Ciolkowskiego 1K, 15‑245 Bialystok, Poland Iwona Misztalewska‑Turkowicz - Faculty of Chemistry, University of Bialystok, Ciolkowskiego 1K, 15‑245 Bialystok, Poland Ewelina Dudź - Faculty of Chemistry, University of Bialystok, Ciolkowskiego 1K, 15‑245 Bialystok, Poland Sylwia Milewska - Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna 37, 15‑361 Bialystok, Poland Paweł Misiak - Faculty of Chemistry, University of Bialystok, Ciolkowskiego 1K, 15‑245 Bialystok, Poland Izabela Kurowska - Faculty of Chemistry, University of Bialystok, Ciolkowskiego 1K, 15‑245 Bialystok, Poland Anna Sadowska - Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna 37, 15‑361 Bialystok, Poland Halina Car - Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna 37, 15‑361 Bialystok, Poland Agnieszka Z. Wilczewska - Faculty of Chemistry, University of Bialystok, Ciolkowskiego 1K, 15‑245 Bialystok, Poland |
Sponsorzy: | This work was fnancially supported by the National Science Centre, Poland, grant no. NCN/2016/21/B/ST5/01365 (AZW). Analyses were performed in the Centre of Synthesis and Analysis BioNanoTechno of the University of Bialystok. The equipment in the Centre was funded by the EU as a part of the Operational Program Development of Eastern Poland 2007–2013, projects: POPW.01.03.00-20-034/09-00 and POPW.01.03.00-20-004/11. |
URI: | http://hdl.handle.net/11320/16606 |
DOI: | 10.1186/s12645-021-00104-9 |
ISSN: | 1868-6966 |
metadata.dc.identifier.orcid: | 0000-0001-8587-6711 |
Typ Dokumentu: | Article |
metadata.dc.rights.uri: | http://creativecommons.org/licenses/by/4.0/ |
Właściciel praw: | © The Author(s), 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. |
Występuje w kolekcji(ach): | Artykuły naukowe (WChem) |
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