Gene regulation with carbon-based siRNA conjugates for cancer therapy

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• 作者：Lingmin Zhang¹ ; Wenfu Zheng¹ ; Rongbing Tang ; Nuoxin Wang ; Wei Zhang ; Xingyu Jiang ; ^{xingyujiang@nanoctr.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Fluorescent carbon nanoparticle ; Gene regulation ; Cancer therapy ; Plk1 gene ; Small interfering RNA
• 刊名：Biomaterials
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：104
• 期：Complete
• 页码：269-278
• 全文大小：2849 K

文摘

We report fluorescent carbon nanoparticle (FCN)-based small interfering RNA (siRNA) conjugates (C-siRNA) for gene regulation and cancer therapy. The C-siRNA has a core of chitosan-derived FCN and a shell of siRNA, and can down-regulate the expression of polo-like kinase-1 (Plk1), a master regulator of mitosis, via siRNA targeting Plk1 (siPlk1), for cancer therapy. The required amount of the FCNs is only ∼1/30 of that of the gold nanoparticles in delivering equal amount of siRNA. The C-siPlk1 led to ∼80% knockdown of cellular Plk1 mRNA in A375 cells, and induced apoptosis of the A375 cells (31.9%) and MCF-7 cells (20.33%), much higher than those by commercial nonviral gene delivery vectors, such as Lipofectamine 2000 in both cell lines (apoptosis rate < 10%). After the C-siPlk1 was administrated to A375 tumor-bearing mice intravenously, the tumor volume was less than 1/11 of the control groups. The C-siRNA can thus be powerful tools for gene delivery and gene therapy.