Targeted-gene silencing of BRAF to interrupt BRAF/MEK/ERK pathway synergized photothermal therapeutics for melanoma using a novel FA-GNR-siBRAF nanosystem.
Nanomedicine
; 14(5): 1679-1693, 2018 07.
Article
en En
| MEDLINE
| ID: mdl-29684526
ABSTRACT
Melanoma is significantly associated with mutant BRAF gene, a suitable target for siRNA-based anti-melanoma therapy. However, a tumor-specific delivery system is a major hurdle for clinical applications. Here, we developed a novel nano-carrier, FA-GNR-siBRAF for safe topical application, which consists of folic acid (FA) as the tumor-targeting moiety, golden nanorods (GNR) providing photothermal capability to kill tumor cells under laser irradiation, and siRNA specifically silencing BRAF (siBRAF). The in vitro and in vivo results revealed that FA-GNR-siBRAF displayed high transfection rates, and subsequently induced remarkable gene knockdown of BRAF, resulting in suppression of melanoma growth due to the interruption of the MEK/ERK pathway. Combinatorial photothermal effects and BRAF knockdown by FA-GNR-siBRAF effectively killed tumor cells through apoptosis, with enhanced efficiency than individual treatments. Therefore, the FA-GNR-siBRAF simultaneously induced BRAF gene silencing and photothermal effects which achieved synergistic efficacy in the treatment of melanoma, paving a new path for developing clinical treatment methods for melanoma.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Melanoma Experimental
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Silenciador del Gen
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ARN Interferente Pequeño
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Nanotubos
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Proteínas Proto-Oncogénicas B-raf
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Ácido Fólico
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Hipertermia Inducida
Límite:
Animals
Idioma:
En
Revista:
Nanomedicine
Asunto de la revista:
BIOTECNOLOGIA
Año:
2018
Tipo del documento:
Article