Targeted-gene silencing of BRAF to interrupt BRAF/MEK/ERK pathway synergized photothermal therapeutics for melanoma using a novel FA-GNR-siBRAF nanosystem.

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.

• 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
• Journal: Nanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 14 Issue 5 Pg. 1679-1693 (07 2018) ISSN: 1549-9642 [Electronic] United States
• PMID: 29684526 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• RNA, Small Interfering
• Gold
• Folic Acid
• Braf protein, mouse
• Proto-Oncogene Proteins B-raf
• Extracellular Signal-Regulated MAP Kinases
• MAP Kinase Kinase 1
• Map2k1 protein, mouse

Topics

• Animals
• Apoptosis
• Combined Modality Therapy
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, genetics)
• Female
• Folic Acid (chemistry)
• Gene Silencing
• Gold (chemistry)
• Hyperthermia, Induced
• MAP Kinase Kinase 1 (antagonists & inhibitors, genetics)
• Melanoma, Experimental (therapy)
• Mice
• Mice, Inbred C57BL
• Nanotubes (chemistry)
• Phototherapy
• Proto-Oncogene Proteins B-raf (antagonists & inhibitors, genetics)
• RNA, Small Interfering (genetics)
• Tumor Cells, Cultured