Delivery of NF-κB shRNA using carbamate-mannose modified PEI for eliminating cancer stem cells.
Nanomedicine
; 14(2): 405-414, 2018 02.
Article
em En
| MEDLINE
| ID: mdl-29175597
ABSTRACT
The presence of cancer stem cells (CSCs) is one of the main reasons that cause cancer relapse and metastasis. In this study, NF-κB shRNA was delivered to target CSCs using carbamate-mannose modified PEI (CMP) as a non-viral gene vector. The polymer was synthesized by blocking primary amine groups of branched PEI (10kDa) through nucleophilic addition between PEI and protected mannose-functionalized cyclic carbonate, followed by mannose deprotection. CMP/control shRNA nanocomplexes showed lower cytotoxicity and higher transfection efficiency in 4T1 murine breast cancer cells than unmodified PEI/control shRNA nanocomplexes. Importantly, CMP/NF-κB shRNA nanocomplexes (CMPN) were capable of inhibiting migration and invasion, decreasing mammosphere and colony formation and lowering ALDH+ CSC population. Furthermore, CMPN not only induced apoptosis and inhibited cell proliferation, but also sensitized the cells to the treatment with doxorubicin-loaded micellar nanoparticles. Therefore, CMPN may provide a promising approach for eliminating CSCs to prevent cancer relapse and metastasis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polietilenoimina
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Células-Tronco Neoplásicas
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Neoplasias da Mama
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Doxorrubicina
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NF-kappa B
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RNA Interferente Pequeno
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Nanopartículas
Limite:
Female
/
Humans
Idioma:
En
Revista:
Nanomedicine
Assunto da revista:
BIOTECNOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Singapura