期刊
BIOMATERIALS
卷 34, 期 4, 页码 1246-1254出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.09.068
关键词
Calcium carbonate; Nanocomposite; Gene therapy; siRNA delivery; AIB1; Bladder cancer
资金
- National Nature Science Foundation of China [30900539]
- Fundamental Research Funds for the Central Universities [09ykpy35]
- Science and Information Technology Foundation of Guangzhou [2011J2200065]
- Guangdong Provincial Science and Technology Foundation [2008B030301112, 2010B031600036]
- National Basic Research Program of China [2010CB934700]
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.
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