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Título: | Mechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomes. |
Autor(es): | Reis, Samara Bonesso dos Silva, Juliana de Oliveira Fossa, Fernanda Garcia Leite, Elaine Amaral Souza, Angelo Malachias de Lana, Gwenaelle Elza Nathalie Pound Mosqueira, Vanessa Carla Furtado Oliveira, Mônica Cristina de Barros, André Luís Branco de Jesus, Marcelo Bispo de |
Palavras-chave: | Drug delivery system |
Data do documento: | 2021 |
Referência: | REIS, S. B. dos et al. Mechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomes. Biomedicine & Pharmacotherapy, v. 134, p. 110952, 2021. Disponível em: <https://www.sciencedirect.com/science/article/pii/S0753332220311446?via%3Dihub>. Acesso em: 10 jun. 2021. |
Resumo: | pH-sensitive liposomes are interesting carriers for drug-delivery, undertaking rapid bilayer destabilization in response to pH changes, allied to tumor accumulation, a desirable behavior in the treatment of cancer cells. Previously, we have shown that pH-sensitive liposomes accumulate in tumor tissues of mice, in which an acidic environment accelerates drug delivery. Ultimately, these formulations can be internalized by tumor cells and take the endosome-lysosomal route. However, the mechanism of doxorubicin release and intracellular traffic of pH-sensitive liposomes remains unclear. To investigate the molecular mechanisms underlying the intracellular release of doxorubicin from pH-sensitive liposomes, we followed HeLa cells viability, internalization, intracel lular trafficking, and doxorubicin’s intracellular delivery mechanisms from pH-sensitive (SpHL-DOX) and non pH-sensitive (nSpHL-DOX) formulations. We found that SpHL-DOX has faster internalization kinetics and intracellular release of doxorubicin, followed by strong nuclear accumulation compared to nSpHL-DOX. The increased nuclear accumulation led to the activation of cleaved caspase-3, which efficiently induced apoptosis. Remarkably, we found that chloroquine and E64d enhanced the cytotoxicity of SpHL-DOX. This knowledge is paramount to improve the efficiency of pH-sensitive liposomes or to be used as a rational strategy for developing new formulations to be applied in vivo. |
URI: | http://www.repositorio.ufop.br/jspui/handle/123456789/14120 |
DOI: | https://doi.org/10.1016/j.biopha.2020.110952 |
ISSN: | 0753-3322 |
Licença: | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Fonte: o PDF do artigo. |
Aparece nas coleções: | DEFAR - Artigos publicados em periódicos |
Arquivos associados a este item:
Arquivo | Descrição | Tamanho | Formato | |
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ARTIGO_MechanisticInsightsIntracellular.pdf | 5,09 MB | Adobe PDF | Visualizar/Abrir |
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