| Texto completo | |
| Autor(es): |
dos Reis, Samara Bonesso
[1]
;
Silva, Juliana de Oliveira
[2]
;
Garcia-Fossa, Fernanda
[1]
;
Leite, Elaine Amaral
[2]
;
Malachias, Angelo
[3]
;
Pound-Lana, Gwenaelle
[4]
;
Furtado Mosqueira, Vanessa Carla
[4]
;
Oliveira, Monica Cristina
[2]
;
Branco de Barros, Andre Luis
[5]
;
de Jesus, Marcelo Bispo
[1]
Número total de Autores: 10
|
| Afiliação do(s) autor(es): | [1] Univ Estadual Campinas, Biol Inst, Dept Biochem & Tissue Biol, Nanocell Interact Lab, Campinas, SP - Brazil
[2] Fed Univ Minas Gerais UFMG, Fac Pharm, Dept Pharmaceut Prod, Belo Horizonte, MG - Brazil
[3] Fed Univ Minas Gerais UFMG, Phys Dept, Belo Horizonte, MG - Brazil
[4] Fed Univ Ouro Preto UFOP, Pharm Sch, Lab Pharmaceut & Nanotechnol LDGNano, Ouro Preto, MG - Brazil
[5] Fed Univ Minas Gerais UFMG, Fac Pharm, Dept Clin & Toxicol Anal, Ave Antonio Carlos 6627, BR-31270910 Belo Horizonte, MG - Brazil
Número total de Afiliações: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | BIOMEDICINE & PHARMACOTHERAPY; v. 134, FEB 2021. |
| Citações Web of Science: | 0 |
| Resumo | |
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, intracellular 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. (AU) | |
| Processo FAPESP: | 14/03002-7 - Internalização e tráfego intracelular de nanopartículas: atividade biológica e perfil nanotoxicológico |
| Beneficiário: | Marcelo Bispo de Jesus |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |
| Processo FAPESP: | 15/06134-4 - EMU concedido no processo 2014/03002-7: leitor multi-modo de imageamento celular (cell imaging multi-mode reader) |
| Beneficiário: | Marcelo Bispo de Jesus |
| Modalidade de apoio: | Auxílio à Pesquisa - Programa Equipamentos Multiusuários |