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http://hdl.handle.net/1843/54509| Type: | Artigo de Periódico |
| Title: | Mechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomes |
| Authors: | Samara Bonesso dos Reis Marcelo Bispo de Jesus Juliana de Oliveira Silva Fernanda Garcia Fossa Elaine Amaral Leite Ângelo Malachias de Souza Gwenaelle Elza Nathalie Pound-Lana Vanessa Carla Furtado Mosqueira Mônica Cristina de Oliveira André Luís Branco de Barros |
| 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. |
| Subject: | Lipossomos Doxorrubicina Sistemas de distribuição de medicamentos |
| language: | eng |
| metadata.dc.publisher.country: | Brasil |
| Publisher: | Universidade Federal de Minas Gerais |
| Publisher Initials: | UFMG |
| metadata.dc.publisher.department: | FAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICAS FAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOS ICX - DEPARTAMENTO DE FÍSICA |
| Rights: | Acesso Aberto |
| metadata.dc.identifier.doi: | https://doi.org/10.1016/j.biopha.2020.110952 |
| URI: | http://hdl.handle.net/1843/54509 |
| Issue Date: | 2021 |
| metadata.dc.url.externa: | https://www.sciencedirect.com/science/article/pii/S0753332220311446 |
| metadata.dc.relation.ispartof: | Biomedicine & Pharmacotherapy |
| Appears in Collections: | Artigo de Periódico |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| Mechanistic insights into the intracellular release of doxorubicin.pdf | 34.42 MB | Adobe PDF | View/Open |
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