Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Bandarra, Susana, Mascarenhas, Paulo, Barahona, Isabel, Nyström, Bo, Calejo, Maria Teresa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480596/
http://dx.doi.org/10.1080/07853890.2021.1896101
Descripción
Sumario: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.