Bioreduction-ruptured nanogel for switch on/off release of Bcl2 siRNA in breast tumor therapy.
J Control Release
; 292: 78-90, 2018 12 28.
Article
em En
| MEDLINE
| ID: mdl-29499219
ABSTRACT
In present study, gene concentrated as well as bioreduction-ruptured nanogel with local enrichment positive charge while low cytotoxicity was developed for Bcl2 siRNA delivery featured in intracellular switch on/off controlled release. Dynamic covalent bond crosslinked nanogel was formed by thiolated PEI of 1.8â¯kDa(PEI-1.8â¯kDa)and biodegradable dextrin. Once nanogel was uptake by tumor cells, high concentration of glutathione (GSH) in cytosol could bioreducible -degrade and rupture the crosslink of this dextrin nanogel (DSP) into hypotoxic PEI-1.8â¯kDa and dextrin, following by burst release of packed siRNA and minimizing the restriction of polymer material for siRNA transcription. This switch on/off siRNA release strategy for gene therapy exhibited equal level of the deregulation of Bcl2 protein expression determined by western blot analysis compared with cationic PEI with 25â¯kDa molecular weight (PEI-25â¯kDa) in vitro. Moreover, the gene concentrated DSP based on hypotoxic PEI-1.8â¯kDa and biodegradable dextrin could be administrated intravenously for systematic therapy on safely. Tumor suppression study of DSP also exhibited a superior antitumor activity in 4T1-luc tumor cell bearing BALB/C mice. Furthermore, it exhibited lower cytotoxicity, almost none hemotoxicity, moreover avoiding recognition and clearance by RES system in healthy mice. Overall, these findings suggest that this reduction-sensitive while bioreduction-ruptured polymer nanogel is an innovative strategy and holds great promise for gene and drug delivery.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas c-bcl-2
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RNA Interferente Pequeno
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Dextrinas
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Nanopartículas
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Neoplasias Mamárias Experimentais
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article