A redox-sensitive, oligopeptide-guided, self-assembling, and efficiency-enhanced (ROSE) system for functional delivery of microRNA therapeutics for treatment of hepatocellular carcinoma
A redox-sensitive, oligopeptide-guided, self-assembling, and efficiency-enhanced (ROSE) system for functional delivery of microRNA therapeutics for treatment of hepatocellular carcinoma
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一种氧化还原敏感、寡肽引导、自组装和效率增强 (ROSE) 系统，用于功能性递送 microRNA 疗法来治疗肝细胞癌。
DOI：
10.1016/j.biomaterials.2016.07.016
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发表时间：
2016-10-01
期刊：
影响因子：
14
通讯作者：
Tang, Guping
中科院分区：
文献类型：
--
作者：
Hu, Qida;Wang, Kai;Tang, Guping
缺乏有效的辅助治疗是肝细胞癌（HCC）复发和转移发生率高的原因。需要一种新的治疗方法用于HCC的辅助治疗。我们开发了一种基于聚合物的纳米系统（ROSE）的功能基因治疗，通过合成超分子复合物自组装从聚阳离子和功能金刚烷模块。将肿瘤抑制剂microRNA-34 a（miR-34 a）治疗剂浓缩的ROSE系统成为ROSE/miR-34 a纳米颗粒，其可以以令人满意的稳定性和效率促进HCC细胞中的基因转染，这可能是由于聚阳离子的质子海绵效应、PEG化保护和通过二硫键断裂的受控释放。同时，在ROSE/miR-34 a中用靶向寡肽SP 94修饰使得在体外对LM 3 HCC细胞的亲和力比肝细胞高，并且在体内具有更高的HCC特异性。此外，ROSE/miR-34 a纳米颗粒显著抑制HCC细胞增殖和体内肿瘤生长，代表了相对于常规基因递送策略的显著效果改善。ROSE/miR-34 a具有氧化还原反应性、寡肽引导的特异性、自组装和增强的转染，因此在未来HCC治疗的辅助治疗中是潜在的治疗剂。(C)2016爱思唯尔有限公司版权所有
Lack of efficient adjuvant therapy contributes to a high incidence of recurrence and metastasis of hepatocellular carcinoma (HCC). A novel therapeutic is required for adjuvant treatment of HCC. We developed a polymer-based nanosystem (ROSE) for functional gene therapy by synthesizing a supra molecular complex self-assembled from polycations and functional adamantyl modules. The ROSE system condensing tumor suppressor microRNA-34a (miR-34a) therapeutics becomes ROSE/miR-34a nanoparticles that could facilitate gene transfection in HCC cells with satisfied stability and efficiency, possibly due to proton sponge effect by polycations, PEGlyation protection, and controlled release by breakdown of disulfide bonds. Meanwhile, modification with a targeting oligopeptide SP94 in ROSE/miR-34a enables approximately higher affinity for LM3 HCC cells than hepatocytes in vitro and greater HCC specificity in vivo. Furthermore, ROSE/miR-34a nanoparticles significantly inhibits HCC cell proliferation and in vivo tumor growth, representing a notable effect improvement over conventional gene delivery strategies. ROSE/miR-34a, featuring redox-responsiveness, oligopeptide-guided specificity, self-assembly, and enhanced transfection, is therefore a potential therapeutic agent in future adjuvant therapy for HCC treatment. (C) 2016 Elsevier Ltd. All rights reserved.