| Full text | |
| Author(s): |
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]
Total Authors: 10
|
| Affiliation: | [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
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | BIOMEDICINE & PHARMACOTHERAPY; v. 134, FEB 2021. |
| Web of Science Citations: | 0 |
| 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, 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) | |
| FAPESP's process: | 14/03002-7 - Internalization and intracellular trafficking of nanoparticles: biological activity and nanotoxicological profile |
| Grantee: | Marcelo Bispo de Jesus |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 15/06134-4 - Multi-User Equipment approved in grant 2014/03002-7: cell imaging multi-mode reader |
| Grantee: | Marcelo Bispo de Jesus |
| Support Opportunities: | Multi-user Equipment Program |