Mechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomes.
dc.contributor.author | Reis, Samara Bonesso dos | |
dc.contributor.author | Silva, Juliana de Oliveira | |
dc.contributor.author | Fossa, Fernanda Garcia | |
dc.contributor.author | Leite, Elaine Amaral | |
dc.contributor.author | Souza, Angelo Malachias de | |
dc.contributor.author | Lana, Gwenaelle Elza Nathalie Pound | |
dc.contributor.author | Mosqueira, Vanessa Carla Furtado | |
dc.contributor.author | Oliveira, Mônica Cristina de | |
dc.contributor.author | Barros, André Luís Branco de | |
dc.contributor.author | Jesus, Marcelo Bispo de | |
dc.date.accessioned | 2021-12-07T21:40:40Z | |
dc.date.available | 2021-12-07T21:40:40Z | |
dc.date.issued | 2021 | pt_BR |
dc.description.abstract | 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. | pt_BR |
dc.identifier.citation | 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. | pt_BR |
dc.identifier.doi | https://doi.org/10.1016/j.biopha.2020.110952 | pt_BR |
dc.identifier.issn | 0753-3322 | |
dc.identifier.uri | http://www.repositorio.ufop.br/jspui/handle/123456789/14120 | |
dc.language.iso | en_US | pt_BR |
dc.rights | aberto | pt_BR |
dc.rights.license | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Fonte: o PDF do artigo. | pt_BR |
dc.subject | Drug delivery system | pt_BR |
dc.title | Mechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomes. | pt_BR |
dc.type | Artigo publicado em periodico | pt_BR |
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