Nanoparticle siRNA against BMI-1 with a Polyethylenimine–Laminarin Conjugate for Gene Therapy in Human Breast Cancer

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• 作者：Xueling Ren ; Lei Liu ; Yuxue Zhou ; Yan Zhu ; Hong Zhang ; Zhenzhong Zhang ; Huixiang Li
• 刊名：Bioconjugate Chemistry
• 出版年：2016
• 出版时间：January 20, 2016
• 年：2016
• 卷：27
• 期：1
• 页码：66-73
• 全文大小：484K
• ISSN：1520-4812

文摘

The B-cell-specific Moloney leukemia virus inset site 1 gene (BMI-1) has attracted considerable attention in recent years because of its key role in breast cancer development and metastasis. The downregulation of BMI-1 expression via small interfering RNA (siRNA) effectively inhibits tumor growth. However, the successful application of this therapy is limited by the unavailability of an appropriate vector for siRNA transfer. Therefore, this study aimed to construct a novel laminarin-based nonviral gene transfer vector to carry a constructed BMI-1-targeting siRNA and to investigate the in vitro and in vivo antitumor effects of this siRNA on breast cancer cells. To enhance the siRNA-carrying capacity, we introduced polyethylenimine (PEI) to laminarin’s surface via N,N′-carbonyldiimidazole, which produced the cationic PEI-modified laminarin conjugate nLP. Subsequent in vitro experiments indicated that nLP not only formed a nanoparticle with a diameter of 200 nm through electrostatic interactions with siRNA but also showed high efficiency (95.0%) in the delivery siRNA to MCF-7 cells. The nanoparticle targeting BMI-1 (nLP/siBMI-2) reduced BMI-1 expression in breast MCF-7 cells by 90.9% reduction. An in vivo tumor suppression experiment demonstrated that the nLP/siBMI-2 nanoparticle had relatively low toxicity and good gene-therapeutic efficacy, with a tumor inhibition rate of 46.6%.