Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 14, Issue 5, Pages 1679-1693Publisher
ELSEVIER
DOI: 10.1016/j.nano.2018.04.010
Keywords
Gold nanorods; BRAF; siRNA; melanoma; photothermal effects
Funding
- Natural Science Foundation of China (NSFC) [81673009]
- Jiangxi Provincial Natural Science Foundation [20161BBG70061, 20151BAB205060]
- Nanchang University Graduate Innovation Fund [CX201639]
- Canadian Institute of Health Research (CIHR)
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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. (C) 2018 Elsevier Inc. All rights reserved.
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