Department of Clinical Biochemistry, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Medical Nanotechnology and Tissue Engineering Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Int J Nanomedicine. 2019 Aug 15;14:6575-6585. doi: 10.2147/IJN.S211844. eCollection 2019.
In a past study, we developed and optimized a novel cationic PEGylated niosome containing anticancer drugs (doxorubicin or quercetin) and siRNA. This study intended to evaluate the anti-tumor effects of the combination therapy to target both the proteins and genes responsible for the development of gastric cancer. CDC20, known as an oncogene, is a good potential therapeutic candidate for gastric cancer.
In order to increase the loading capacity of siRNA and achieve appropriate physical properties, we optimized the cationic PEGylated niosome in terms of the amount of the cationic lipids. Drugs (doxorubicin and quercetin) and CDC20siRNA were loaded into the co-delivery system, and physical characteristics, thermosensitive controlled-release, gene silencing efficiency, and apoptosis rate were determined.
The results showed that the designed co-delivery system for the drugs and gene silencer had an appropriate size and a high positive charge for loading siRNA, and also showed a thermosensitive drug release behavior, which successfully silenced the CDC20 expression when compared with the single delivery of siRNA or the drug. Moreover, the co-delivery of drugs and CDC20siRNA exhibited a highly inhibitory property for the cell growth of gastric cancer cells.
It seems that the novel cationic PEGylated niosomes co-loaded with anticancer drug and CDC20siRNA has a promising application for the treatment of gastric cancer.
在过去的研究中,我们开发并优化了一种新型阳离子 PEG 化泡囊,其中包含抗癌药物(多柔比星或槲皮素)和 siRNA。本研究旨在评估针对导致胃癌发生的蛋白质和基因的联合治疗的抗肿瘤作用。CDC20 作为一种癌基因,是治疗胃癌的一个很好的潜在治疗候选物。
为了增加 siRNA 的载药量并达到适当的物理性质,我们优化了阳离子 PEG 化泡囊的阳离子脂质的用量。将药物(多柔比星和槲皮素)和 CDC20siRNA 载入共递药系统,测定其物理特性、热敏控制释放、基因沉默效率和细胞凋亡率。
结果表明,设计的药物和基因沉默剂共递药系统具有适当的粒径和较高的正电荷载药量,并且具有热敏药物释放行为,与单独递送 siRNA 或药物相比,成功地沉默了 CDC20 的表达。此外,药物和 CDC20siRNA 的共递送对胃癌细胞的生长具有高度抑制作用。
新型阳离子 PEG 化泡囊共载抗癌药物和 CDC20siRNA 似乎具有治疗胃癌的应用前景。