The inhibition of human bladder cancer growth by calcium carbonate/CaIP6 nanocomposite particles delivering AIB1 siRNA
The inhibition of human bladder cancer growth by calcium carbonate/CaIP6 nanocomposite particles delivering AIB1 siRNA
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碳酸钙/CaIP6纳米复合颗粒递送AIB1 siRNA抑制人膀胱癌生长
DOI：
10.1016/j.biomaterials.2012.09.068
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发表时间：
2013-01-01
期刊：
影响因子：
14
通讯作者：
Luo, Junhang
中科院分区：
文献类型：
--
作者：
Wei, Jinhuan;Cheang, Tuckyun;Luo, Junhang
以前，我们报道了无机无定形碳酸钙（ACC）杂化纳米球功能化的Ca（II）-IP 6化合物（CaIP 6）是一个有前途的基因载体在体外。在这里，非病毒基因载体，ACC/CaIP 6纳米复合颗粒（NPACC/CaIP 6），有效地在体外和体内传递的小干扰RNA（siRNA）靶向人扩增的乳腺癌1（AIB 1）进行了评估。该纳米颗粒能够形成ACC/CaIP 6纳米颗粒-siRNA复合物，并以高转染效率将siRNA转移到靶细胞中。ACC/CaIP 6纳米粒子-siRNA复合物对人膀胱癌124细胞无明显的细胞毒性。ACC/CaIP 6/siRNA复合物转染AIB 1基因后，AIB 1基因表达下调，细胞增殖抑制，凋亡诱导，细胞周期阻滞。NPACC/CaIP 6/siAIB 1具有良好的组织穿透性，瘤内注射NPACC/CaIP 6/siAIB 1可抑制肿瘤生长，下调PI 3 K/Akt信号通路。我们的结论是，ACC/CaIP 6纳米粒子是一个有前途的系统，有效地传递siRNA的癌症基因治疗。(C)2012爱思唯尔有限公司保留所有权利。
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 124 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/CalP6/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. (C) 2012 Elsevier Ltd. All rights reserved.