Targeted Gene Silencing BRAF Synergized Photothermal Effect Inhibits Hepatoma Cell Growth Using New GAL-GNR-siBRAF Nanosystem
Targeted Gene Silencing BRAF Synergized Photothermal Effect Inhibits Hepatoma Cell Growth Using New GAL-GNR-siBRAF Nanosystem
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使用新型 GAL-GNR-siBRAF 纳米系统靶向基因沉默 BRAF 协同光热效应抑制肝癌细胞生长
DOI：
10.1186/s11671-020-03340-x
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发表时间：
2020-05
影响因子：
--
通讯作者：
Min Weiping
中科院分区：
文献类型：
--
作者：
Liu Yanling;Tan Manman;Zhang Yujuan;Huang Wei;Min Liangliang;Peng Shanshan;Yuan Keng;Qiu Li;Min Weiping
肝癌是世界范围内最常见的恶性肿瘤之一。RAF激酶抑制剂可有效治疗肝细胞癌（HCC），因此抑制BRAF/MEK/ERK途径已成为新型肝癌治疗的新治疗策略。然而，肿瘤靶向给药系统的研究仍然是临床应用的重要障碍。半乳糖（GAL）可以靶向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的多功能纳米材料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，siRNA特异性沉默BRAF（siBRAF）。纳米载体GAL-GNR-siBRAF具有较高的siRNA负载量，并能抑制siRNA在血清中的降解。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，组合光热效应和GAL-GNR-siBRAF的BRAF敲低有效地引起肿瘤细胞死亡。因此，我们的研究开发了一种新型靶向多功能纳米材料GAL-GNR-siBRAF用于肝癌的治疗，为临床新治疗方法的开发提供了思路。
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.
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影响因子：
5.3
作者：
通讯作者：
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肿瘤 SOCS3 甲基化状态预测 HCC 患者对 TACE 的治疗反应和预后
影响因子：
--
作者：
Jiang BG;Wang N;Huang J;Yang Y;Sun LL;Pan ZY;Zhou WP
通讯作者：
Zhou WP
影响因子：
4.9
作者：
Navarro G;Pan J;Torchilin VP
通讯作者：
Torchilin VP
DOI：
10.1016/j.critrevonc.2015.10.015
发表时间：
2016-02
期刊：
Critical reviews in oncology/hematology
影响因子：
--
作者：
Samuel Wang Sherng Young;M. Stenzel;Jia-Lin Yang
通讯作者：
Samuel Wang Sherng Young;M. Stenzel;Jia-Lin Yang
影响因子：
2.1
作者：
V. Mukthinuthalapati;Yuchen Wang;Yazan Abu Omar;M. Syed;B. Attar
通讯作者：
V. Mukthinuthalapati;Yuchen Wang;Yazan Abu Omar;M. Syed;B. Attar