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Cytotoxicity of temperature-responsive cationic diblock copolymers in human cancer and non-cancer cells lines
INTRODUCTION: Thermoresponsive polymers have been widely investigated in modern drug delivery and gene delivery systems, due to their potential to load and release the payload by simply modifying local temperature [1]. Previous work by some of us has shown that the thermoresponsive copolymers poly(N...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480596/ http://dx.doi.org/10.1080/07853890.2021.1896101 |
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author | Bandarra, Susana Mascarenhas, Paulo Barahona, Isabel Nyström, Bo Calejo, Maria Teresa |
author_facet | Bandarra, Susana Mascarenhas, Paulo Barahona, Isabel Nyström, Bo Calejo, Maria Teresa |
author_sort | Bandarra, Susana |
collection | PubMed |
description | INTRODUCTION: Thermoresponsive polymers have been widely investigated in modern drug delivery and gene delivery systems, due to their potential to load and release the payload by simply modifying local temperature [1]. Previous work by some of us has shown that the thermoresponsive copolymers poly(N-isopropylacrylamide)(n)-block-poly((3-acrylamidopropyl) trimethylammonium chloride)(m) (PNIPAAM(n)-b-PAMPTMA(+)(m)) can efficiently deliver DNA and siRNA to HeLa [2] and HT1080 cells [3]. The transfection efficiency and cytotoxicity were highly dependent on the length and ratio of the two blocks (n:m) [2,3]. In anticancer therapy, such polymers may be able to deliver drugs precisely at the tumour site by local and transient thermal treatment [1]. Having this in mind, in this work, we took the first step towards expanding the scope of use of the PNIPAAM(n)-b-PAMPTMA(+)(m) copolymers by investigating their cytotoxicity in human cancer cell lines and in a normal breast cell line. MATERIALS AND METHODS: The copolymers (n:m ratio 48:6, 48:10 and 65:20) were dissolved in varying concentrations in cell culture medium, as described before [2] and were incubated at 37 °C with each of the tested cell lines for 6 h. After that, the medium was replaced, and the cells were incubated for 48 h/37 °C. The viability of cells was measured by the MTT cytotoxicity assay. Untreated cells were used as negative control (representing 100% viability). Cell lines: HeLa (cervical cancer), HCC1806 (breast cancer) and MCF10A (non-tumorigenic breast epithelial cell line). RESULTS: In this preliminary study the cytotoxicity of the PNIPAAM(n)-b-PAMPTMA(m)(+) copolymers was shown to be dependent on the polymer concentration, n:m ratio and cell line. MCF10A cells were very tolerant to the presence of the copolymer 48:6, even at the highest concentration (Figure 1), followed by HeLa and HCC1806. Discussion and conclusions: The low toxicity shown particularly for the non-tumorigenic cell line but higher toxicity towards the cancer cell lines makes the tested copolymers highly appealing as drug carriers in anti-cancer therapy. |
format | Online Article Text |
id | pubmed-8480596 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-84805962022-03-03 Cytotoxicity of temperature-responsive cationic diblock copolymers in human cancer and non-cancer cells lines Bandarra, Susana Mascarenhas, Paulo Barahona, Isabel Nyström, Bo Calejo, Maria Teresa Ann Med Abstract 202 INTRODUCTION: Thermoresponsive polymers have been widely investigated in modern drug delivery and gene delivery systems, due to their potential to load and release the payload by simply modifying local temperature [1]. Previous work by some of us has shown that the thermoresponsive copolymers poly(N-isopropylacrylamide)(n)-block-poly((3-acrylamidopropyl) trimethylammonium chloride)(m) (PNIPAAM(n)-b-PAMPTMA(+)(m)) can efficiently deliver DNA and siRNA to HeLa [2] and HT1080 cells [3]. The transfection efficiency and cytotoxicity were highly dependent on the length and ratio of the two blocks (n:m) [2,3]. In anticancer therapy, such polymers may be able to deliver drugs precisely at the tumour site by local and transient thermal treatment [1]. Having this in mind, in this work, we took the first step towards expanding the scope of use of the PNIPAAM(n)-b-PAMPTMA(+)(m) copolymers by investigating their cytotoxicity in human cancer cell lines and in a normal breast cell line. MATERIALS AND METHODS: The copolymers (n:m ratio 48:6, 48:10 and 65:20) were dissolved in varying concentrations in cell culture medium, as described before [2] and were incubated at 37 °C with each of the tested cell lines for 6 h. After that, the medium was replaced, and the cells were incubated for 48 h/37 °C. The viability of cells was measured by the MTT cytotoxicity assay. Untreated cells were used as negative control (representing 100% viability). Cell lines: HeLa (cervical cancer), HCC1806 (breast cancer) and MCF10A (non-tumorigenic breast epithelial cell line). RESULTS: In this preliminary study the cytotoxicity of the PNIPAAM(n)-b-PAMPTMA(m)(+) copolymers was shown to be dependent on the polymer concentration, n:m ratio and cell line. MCF10A cells were very tolerant to the presence of the copolymer 48:6, even at the highest concentration (Figure 1), followed by HeLa and HCC1806. Discussion and conclusions: The low toxicity shown particularly for the non-tumorigenic cell line but higher toxicity towards the cancer cell lines makes the tested copolymers highly appealing as drug carriers in anti-cancer therapy. Taylor & Francis 2021-09-28 /pmc/articles/PMC8480596/ http://dx.doi.org/10.1080/07853890.2021.1896101 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Abstract 202 Bandarra, Susana Mascarenhas, Paulo Barahona, Isabel Nyström, Bo Calejo, Maria Teresa Cytotoxicity of temperature-responsive cationic diblock copolymers in human cancer and non-cancer cells lines |
title | Cytotoxicity of temperature-responsive cationic diblock copolymers in human cancer and non-cancer cells lines |
title_full | Cytotoxicity of temperature-responsive cationic diblock copolymers in human cancer and non-cancer cells lines |
title_fullStr | Cytotoxicity of temperature-responsive cationic diblock copolymers in human cancer and non-cancer cells lines |
title_full_unstemmed | Cytotoxicity of temperature-responsive cationic diblock copolymers in human cancer and non-cancer cells lines |
title_short | Cytotoxicity of temperature-responsive cationic diblock copolymers in human cancer and non-cancer cells lines |
title_sort | cytotoxicity of temperature-responsive cationic diblock copolymers in human cancer and non-cancer cells lines |
topic | Abstract 202 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480596/ http://dx.doi.org/10.1080/07853890.2021.1896101 |
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