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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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