The inhibition of human bladder cancer growth by calcium carbonate/CaIP6 nanocomposite particles delivering AIB1 siRNA

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• 作者：Jinhuan Wei^a ; ¹ ; Tuckyun Cheang^b ; ¹ ; Bing Tang^b ; ¹ ; Haoming Xia^b ; Zhouhao Xing^c ; Zhenhua Chen^a ; Yong Fang^a ; Wei Chen^a ; Anwu Xu^c ; ^{anwuxu@ustc.edu.cn} ; Shenming Wang^b ; ^{shenmingwang@vip.sohu.com} ; Junhang Luo^a ; ^{luojunh@mail.sysu.edu.cn}
• 关键词：Calcium carbonate ; Nanocomposite ; Gene therapy ; siRNA delivery ; AIB1 ; Bladder cancer
• 刊名：Biomaterials
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：34
• 期：4
• 页码：1246-1254
• 全文大小：1511 K

文摘

Previously, we reported that inorganic amorphous calcium carbonate (ACC) hybrid nanospheres functionalized with Ca(II)-IP6 compound (CaIP6) is a promising gene vector in?vitro. Here, nonviral gene carrier, ACC/CaIP6 nanocomposite particles (NPACC/CaIP6), was evaluated for efficient in?vitro and in?vivo delivery of small interfering RNA (siRNA) targeting human Amplified in breast cancer 1 (AIB1). The nanoparticle is capable of forming ACC/CaIP6 nanoparticle-siRNA complexes and transferring siRNA into targeted cells with high transfection efficiency. Meanwhile the ACC/CaIP6 nanoparticle-siRNA complexes have no obvious cytotoxicity for human bladder cancer T24 cells. Furthermore, NPACC/CaIP6 effectively protected the encapsulated siRNA from degradation, AIB1 knockdown mediated by ACC/CaIP6/siRNA complexes transfection resulted in cells proliferation inhibition, apoptosis induction and cell cycle arrest in?vitro. NPACC/CaIP6 exhibited well tissues penetrability in localized siRNA delivering, intratumoral injection of NPACC/CaIP6/siAIB1 could attenuate tumor growth and downregulation of PI3K/Akt signaling pathway in?vivo. We conclude that ACC/CaIP6 nanoparticle is a promising system for effective delivery of siRNA for cancer gene therapy.