Polyamine metabolism-based dual functional gene delivery system to synergistically inhibit the proliferation of cancer
Polyamine metabolism-based dual functional gene delivery system to synergistically inhibit the proliferation of cancer
复制标题
基于多胺代谢的双功能基因传递系统协同抑制癌症增殖
DOI：
10.1016/j.ijpharm.2016.04.039
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发表时间：
2016-06-15
影响因子：
5.8
通讯作者：
Jiang, Hu-Lin
中科院分区：
文献类型：
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作者：
Cui, Peng-Fei;Xing, Lei;Jiang, Hu-Lin
与肿瘤生长相关的多胺含量受鸟氨酸脱羧酶和S-腺苷蛋氨酸脱羧酶的调节，这两种酶是多胺生物合成的关键酶。在这里，我们的目标是开发一种基于多胺类似物的pH响应型阳离子聚(胍丁胺)，它既可以作为基因载体，又可以通过抑制细胞内降解后的ODC来作为抗癌剂。以聚胍丁胺/SAMDC siRNA复合体为核心形成的核壳纳米粒包覆牛血清白蛋白，具有更好的体内循环稳定性和肿瘤靶向性。当纳米粒通过内吞作用被肿瘤细胞摄取并在内体中降解时，释放的胍丁胺和SAMDC siRNA可以协同抑制多胺的生物合成，从而抑制肿瘤的生长。我们的研究为基于多胺代谢的肿瘤治疗提供了一条潜在的途径。(C)2016爱思唯尔B.V.保留所有权利。
Polyamine content, which is associated with tumor growth, can be regulated by ornithine decarboxylase (ODC) and S-adenosyl methionine decarboxylase (SAMDC), two key enzymes in polyamine biosynthesis. Here we aim to develop a pH-responsive cationic poly(agmatine) based on a polyamine analogue-agmatine that can dually function as a gene delivery vector as well as an anticancer agent by inhibiting ODC after intracellular degradation. The core-shell nanoparticles, formed by poly(agmatine)/SAMDC siRNA complex as a core, were coated with bovine serum albumin for better in vivo circulation stability and tumor targeting. When the nanoparticles were taken up by tumor cells via endocytosis and degraded in endosome, the released agmatine and SAMDC siRNA can synergistically inhibit polyamines biosynthesis, inducing inhibition of tumor proliferation. Our study offered a potential way in tumor therapy based on polyamine metabolism. (c) 2016 Elsevier B.V. All rights reserved.