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

Abstract 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 vitr...

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Bibliographic Details
Published in:Biomaterials 2013-01, Vol.34 (4), p.1246-1254
Main Authors: Wei, Jinhuan, Cheang, Tuckyun, Tang, Bing, Xia, Haoming, Xing, Zhouhao, Chen, Zhenhua, Fang, Yong, Chen, Wei, Xu, Anwu, Wang, Shenming, Luo, Junhang
Format: Article
Language:English
Subjects:
Advanced Basic Science
AIB1
Animals
Biomedical materials
Bladder
Bladder cancer
Calcium carbonate
Calcium Carbonate - chemistry
Cancer
Cell Line, Tumor
Dentistry
Female
Gene therapy
Human
Humans
In vitro testing
In vivo tests
Inhibition
Mice
Nanocapsules - administration & dosage
Nanocapsules - chemistry
Nanocomposite
Nanostructure
RNA, Small Interfering - administration & dosage
RNA, Small Interfering - chemistry
siRNA delivery
Surgical implants
Treatment Outcome
Urinary Bladder Neoplasms - drug therapy
Urinary Bladder Neoplasms - genetics
Urinary Bladder Neoplasms - therapy
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Summary:Abstract 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.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2012.09.068