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spelling 2023-06-05T16:30:52Z2023-06-05T16:30:52Z2021134110https://doi.org/10.1016/j.biopha.2020.1109521950-6007http://hdl.handle.net/1843/54509https://orcid.org/0000-0003-0812-1491https://orcid.org/0000-0003-2308-0149https://orcid.org/0000-0001-8812-3811https://orcid.org/0000-0002-8703-4283https://orcid.org/0000-0002-0368-6090https://orcid.org/0000-0002-7641-6585CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorFAPESP - Fundação de Amparo à Pesquisa do Estado de São PauloPH-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.engUniversidade Federal de Minas GeraisUFMGBrasilFAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICASFAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOSICX - DEPARTAMENTO DE FÍSICABiomedicine & PharmacotherapyLipossomosDoxorrubicinaSistemas de distribuição de medicamentosPH-sensitive liposomeDoxorubicinDrug delivery systemIntracellular releaseMechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.sciencedirect.com/science/article/pii/S0753332220311446Samara Bonesso dos ReisMarcelo Bispo de JesusJuliana de Oliveira SilvaFernanda Garcia FossaElaine Amaral LeiteÂngelo Malachias de SouzaGwenaelle Elza Nathalie Pound-LanaVanessa Carla Furtado MosqueiraMônica Cristina de OliveiraAndré Luís Branco de Barrosapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINALMechanistic insights into the intracellular release of doxorubicin.pdfMechanistic insights into the intracellular release of doxorubicin.pdfapplication/pdf35249383https://repositorio.ufmg.br/bitstream/1843/54509/2/Mechanistic%20insights%20into%20the%20intracellular%20release%20of%20doxorubicin.pdf7fbc6bccbec7954a7601732c02094f4aMD52LICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/54509/1/License.txtfa505098d172de0bc8864fc1287ffe22MD511843/545092023-06-05 16:35:36.726oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-06-05T19:35:36Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
dc.title.pt_BR.fl_str_mv Mechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomes
title Mechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomes
spellingShingle Mechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomes
Samara Bonesso dos Reis
PH-sensitive liposome
Doxorubicin
Drug delivery system
Intracellular release
Lipossomos
Doxorrubicina
Sistemas de distribuição de medicamentos
title_short Mechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomes
title_full Mechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomes
title_fullStr Mechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomes
title_full_unstemmed Mechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomes
title_sort Mechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomes
author Samara Bonesso dos Reis
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv 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
dc.subject.por.fl_str_mv PH-sensitive liposome
Doxorubicin
Drug delivery system
Intracellular release
topic PH-sensitive liposome
Doxorubicin
Drug delivery system
Intracellular release
Lipossomos
Doxorrubicina
Sistemas de distribuição de medicamentos
dc.subject.other.pt_BR.fl_str_mv Lipossomos
Doxorrubicina
Sistemas de distribuição de medicamentos
description CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
publishDate 2021
dc.date.issued.fl_str_mv 2021
dc.date.accessioned.fl_str_mv 2023-06-05T16:30:52Z
dc.date.available.fl_str_mv 2023-06-05T16:30:52Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1843/54509
dc.identifier.doi.pt_BR.fl_str_mv https://doi.org/10.1016/j.biopha.2020.110952
dc.identifier.issn.pt_BR.fl_str_mv 1950-6007
dc.identifier.orcid.pt_BR.fl_str_mv https://orcid.org/0000-0003-0812-1491
https://orcid.org/0000-0003-2308-0149
https://orcid.org/0000-0001-8812-3811
https://orcid.org/0000-0002-8703-4283
https://orcid.org/0000-0002-0368-6090
https://orcid.org/0000-0002-7641-6585
url https://doi.org/10.1016/j.biopha.2020.110952
http://hdl.handle.net/1843/54509
https://orcid.org/0000-0003-0812-1491
https://orcid.org/0000-0003-2308-0149
https://orcid.org/0000-0001-8812-3811
https://orcid.org/0000-0002-8703-4283
https://orcid.org/0000-0002-0368-6090
https://orcid.org/0000-0002-7641-6585
identifier_str_mv 1950-6007
dc.language.iso.fl_str_mv eng
language eng
dc.relation.ispartof.none.fl_str_mv Biomedicine & Pharmacotherapy
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Minas Gerais
dc.publisher.initials.fl_str_mv UFMG
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv FAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICAS
FAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOS
ICX - DEPARTAMENTO DE FÍSICA
publisher.none.fl_str_mv Universidade Federal de Minas Gerais
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFMG
instname:Universidade Federal de Minas Gerais (UFMG)
instacron:UFMG
instname_str Universidade Federal de Minas Gerais (UFMG)
instacron_str UFMG
institution UFMG
reponame_str Repositório Institucional da UFMG
collection Repositório Institucional da UFMG
bitstream.url.fl_str_mv https://repositorio.ufmg.br/bitstream/1843/54509/2/Mechanistic%20insights%20into%20the%20intracellular%20release%20of%20doxorubicin.pdf
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