Blockade of HIF-1α and STAT3 by hyaluronate-conjugated TAT-chitosan-SPION nanoparticles loaded with siRNA molecules prevents tumor growth.
Nanomedicine
; 34: 102373, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33667724
ABSTRACT
HIF-1α and STAT3 are two of the critical factors in the growth, proliferation, and metastasis of cancer cells and play a crucial role in inhibiting anti-cancer immune responses. Therefore, we used superparamagnetic iron oxide (SPION) nanoparticles (NPs) coated with thiolated chitosan (ChT) and trimethyl chitosan (TMC) and functionalized with hyaluronate (H) and TAT peptide for delivery of siRNA molecules against STAT3 and HIF-1α to cancer cells both in vivo and in vitro. The results indicated that tumor cell transfection with siRNA-encapsulated NPs robustly inhibited proliferation and migration and induced apoptosis in tumor cells. Furthermore, simultaneous silencing of HIF-1α and STAT3 significantly repressed cancer development in two different tumor types (4T1 breast cancer and CT26 colon cancer) which were associated with upregulation of cytotoxic T lymphocytes and IFN-γ secretion. The findings suggest inhibiting the HIF-1α/STAT3 axis by SPION-TMC-ChT-TAT-H NPs as an effective way to treat cancer.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Neoplasias do Colo
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RNA Interferente Pequeno
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Quitosana
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Proliferação de Células
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Fator de Transcrição STAT3
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Subunidade alfa do Fator 1 Induzível por Hipóxia
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Nanopartículas Magnéticas de Óxido de Ferro
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Ácido Hialurônico
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Nanomedicine
Assunto da revista:
BIOTECNOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Indonésia