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Int J Nanomedicine ; 13: 1241-1256, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29535520

RESUMEN

INTRODUCTION: MicroRNA-155 (miR-155) is an oncogenic microRNA, which is upregulated in many human cancers including colorectal cancer (CRC). Overexpression of miR-155 has been found to regulate several cancer-related pathways, and therefore, targeting miR-155 may be an effective strategy for cancer therapy. However, effective and safe delivery of anti-miR-155 to tumors remains challenging for the clinical applications of anti-miR-155-based therapeutics. METHODS: In this study, we explored the expression of miR-155 and the transcription factor nuclear factor kappa B (NF-κB) in CRC tissues and cell lines, and the possible relationship between miR-155 and NF-κB. We further report on anti-miR-155-loaded mesoporous silica nanoparticles (MSNs) modified with polymerized dopamine (PDA) and AS1411 aptamer (MSNs-anti-miR-155@PDA-Apt) for the targeted treatment of CRC. RESULTS: Results showed that miR-155 is overexpressed in CRC tissues and cell lines, and there is a positive feedback loop between NF-κB and miR-155. Compared to the control groups, MSNs-anti-miR-155@PDA-Apt could efficiently downregulate miR-155 expression in SW480 cells and achieve significantly high targeting efficiency and enhanced therapeutic effects in both in vivo and in vitro experiments. Furthermore, inhibition of miR-155 by MSNs-anti-miR-155@PDA-Apt can enhance the sensitivity of SW480 to 5-fluorouracil chemotherapy. CONCLUSION: Thus, our results suggested that MSNs-anti-miR-155@PDA-Apt is a promising nanoformulation for CRC treatment.


Asunto(s)
Antagomirs/administración & dosificación , Neoplasias Colorrectales/terapia , Sistemas de Liberación de Medicamentos/métodos , MicroARNs/administración & dosificación , Nanopartículas/administración & dosificación , Animales , Antimetabolitos Antineoplásicos/farmacología , Línea Celular Tumoral , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Femenino , Fluorouracilo/farmacología , Regulación Neoplásica de la Expresión Génica , Terapia Genética/métodos , Humanos , Indoles/química , Ratones Endogámicos BALB C , MicroARNs/genética , FN-kappa B/genética , FN-kappa B/metabolismo , Nanopartículas/química , Polímeros/química , Dióxido de Silicio/química , Ensayos Antitumor por Modelo de Xenoinjerto
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