Mechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomes

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dc.creatorSamara Bonesso dos Reis
dc.creatorMarcelo Bispo de Jesus
dc.creatorJuliana de Oliveira Silva
dc.creatorFernanda Garcia Fossa
dc.creatorElaine Amaral Leite
dc.creatorÂngelo Malachias de Souza
dc.creatorGwenaelle Elza Nathalie Pound-Lana
dc.creatorVanessa Carla Furtado Mosqueira
dc.creatorMônica Cristina de Oliveira
dc.creatorAndré Luís Branco de Barros
dc.date.accessioned2023-06-05T16:30:52Z
dc.date.accessioned2025-09-09T00:14:23Z
dc.date.available2023-06-05T16:30:52Z
dc.date.issued2021
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.description.sponsorshipFAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulo
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.1016/j.biopha.2020.110952
dc.identifier.issn1950-6007
dc.identifier.urihttps://hdl.handle.net/1843/54509
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofBiomedicine & Pharmacotherapy
dc.rightsAcesso Aberto
dc.subjectLipossomos
dc.subjectDoxorrubicina
dc.subjectSistemas de distribuição de medicamentos
dc.subject.otherPH-sensitive liposome
dc.subject.otherDoxorubicin
dc.subject.otherDrug delivery system
dc.subject.otherIntracellular release
dc.titleMechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomes
dc.typeArtigo de periódico
local.citation.epage10
local.citation.spage1
local.citation.volume134
local.description.resumoPH-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.
local.identifier.orcidhttps://orcid.org/0000-0003-0812-1491
local.identifier.orcidhttps://orcid.org/0000-0003-2308-0149
local.identifier.orcidhttps://orcid.org/0000-0001-8812-3811
local.identifier.orcidhttps://orcid.org/0000-0002-8703-4283
local.identifier.orcidhttps://orcid.org/0000-0002-0368-6090
local.identifier.orcidhttps://orcid.org/0000-0002-7641-6585
local.publisher.countryBrasil
local.publisher.departmentFAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICAS
local.publisher.departmentFAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOS
local.publisher.departmentICX - DEPARTAMENTO DE FÍSICA
local.publisher.initialsUFMG
local.url.externahttps://www.sciencedirect.com/science/article/pii/S0753332220311446

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