Targeted-gene silencing of BRAF to interrupt BRAF/MEK/ERK pathway synergized photothermal therapeutics for melanoma using a novel FA-GNR-siBRAF nanosystem |
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Authors: | Yujuan Zhang Xuelin Zhan Shanshan Peng Ying Cai Yu Shrike Zhang Yanling Liu Zhigang Wang Yanrong Yu Yifan Wang Qiaofa Shi Xiaoping Zeng Keng Yuan Nanjin Zhou Rakesh Joshi Meng Zhang Zhuxu Zhang Weiping Min |
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Affiliation: | 1. Institute of immunotherapy and College of Basic Medicine of Nanchang University, and Jiangxi Academy of Medical Sciences, Nanchang, China;2. Jiangxi Provincial Key Laboratory of Immunotherapy, Nanchang, China;3. Department of Surgery, Pathology and Oncology, University of Western Ontario, London, Canada;4. Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women''s Hospital, Harvard Medical School, Cambridge, MA, USA |
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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. |
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Keywords: | GNR gold nanorods siRNA small interfering RNA siBRAF siRNA specific for BRAF FA folic acid CTAB cetyltrimethylammonium bromide MUA mercaptoundecanoic acid PEI polyethylene imine TEM transmission electron microscope NMR nuclear magnetic resonance LSPR localized surface plasmon resonance PTT photothermal therapy Gold nanorods BRAF siRNA melanoma photothermal effects |
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