Liu Yanling, Tan Manman, Zhang Yujuan, Huang Wei, Min Liangliang, Peng Shanshan, Yuan Keng, Qiu Li, Min Weiping
Institute of Immunotherapy, Nanchang University, Nanchang, 330006, Jiangxi, China.
Jiangxi University of Technology, Nanchang, Jiangxi, 330098, China.
Nanoscale Res Lett. 2020 May 24;15(1):116. doi: 10.1186/s11671-020-03340-x.
Liver cancer is one of the most common malignancies worldwide. The RAF kinase inhibitors are effective in the treatment of hepatocellular carcinoma (HCC); therefore, inhibition of the BRAF/MEK/ERK pathway has become a new therapeutic strategy for novel HCC therapy. However, targeted specific delivery systems for tumors are still significant obstacle to clinical applications. Galactose (GAL) can target the asialoglycoprotein receptor (ASGPR) that is highly expressed on liver cancer cells. In this study, we designed a novel multifunctional nanomaterial GAL-GNR-siBRAF which consists of three parts, GAL as the liver cancer-targeting moiety, golden nanorods (GNR) offering photothermal capability under near infrared light, and siRNA specifically silencing BRAF (siBRAF). The nanocarrier GAL-GNR-siBRAF showed high siRNA loading capacity and inhibited the degradation of siRNA in serum. Compared with naked gold nanorods, GAL-GNR-siBRAF possessed lower biotoxicity and higher efficacy of gene silencing. Treatment with GAL-GNR-siBRAF significantly downregulated the expression of BRAF and impaired proliferation, migration, and invasion of liver cancer cells. Moreover, combinatorial photothermal effects and BRAF knockdown by GAL-GNR-siBRAF effectively given rise to tumor cell death. Therefore, our study developed a new type of targeted multi-functional nanomaterial GAL-GNR-siBRAF for the treatment of liver cancer, which provides ideas for the development of new clinical treatment methods.
肝癌是全球最常见的恶性肿瘤之一。RAF激酶抑制剂在肝细胞癌（HCC）治疗中有效；因此，抑制BRAF/MEK/ERK通路已成为新型HCC治疗的一种新策略。然而，肿瘤靶向特异性递送系统仍是临床应用的重大障碍。半乳糖（GAL）可靶向在肝癌细胞上高表达的去唾液酸糖蛋白受体（ASGPR）。在本研究中，我们设计了一种新型多功能纳米材料GAL-GNR-siBRAF，它由三部分组成，GAL作为肝癌靶向部分，金纳米棒（GNR）在近红外光下提供光热能力，以及特异性沉默BRAF的小干扰RNA（siBRAF）。纳米载体GAL-GNR-siBRAF显示出高siRNA负载能力，并抑制血清中siRNA的降解。与裸金纳米棒相比，GAL-GNR-siBRAF具有更低的生物毒性和更高的基因沉默效率。用GAL-GNR-siBRAF处理可显著下调BRAF的表达，并损害肝癌细胞的增殖、迁移和侵袭。此外，GAL-GNR-siBRAF的组合光热效应和BRAF基因敲低有效导致肿瘤细胞死亡。因此，我们的研究开发了一种用于治疗肝癌的新型靶向多功能纳米材料GAL-GNR-siBRAF，为新的临床治疗方法的开发提供了思路
