Reis, Samara Bonesso dosSilva, Juliana de OliveiraFossa, Fernanda GarciaLeite, Elaine AmaralSouza, Angelo Malachias deLana, Gwenaelle Elza Nathalie PoundMosqueira, Vanessa Carla FurtadoOliveira, Mônica Cristina deBarros, André Luís Branco deJesus, Marcelo Bispo de2021-12-072021-12-072021REIS, 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. 2021.0753-3322http://www.repositorio.ufop.br/jspui/handle/123456789/14120pH-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.en-USabertoDrug delivery systemArtigo publicado em periodicoThis is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Fonte: o PDF do artigo.https://doi.org/10.1016/j.biopha.2020.110952