title: 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 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.
authors.affiliation: Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Jinhuan
authors.initials: J
authors.lastname: Wei
authors.forename: Tuckyun
authors.initials: T
authors.lastname: Cheang
authors.forename: Bing
authors.initials: B
authors.lastname: Tang
authors.forename: Haoming
authors.initials: H
authors.lastname: Xia
authors.forename: Zhouhao
authors.initials: Z
authors.lastname: Xing
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: Fang
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Anwu
authors.initials: A
authors.lastname: Xu
authors.forename: Shenming
authors.initials: S
authors.lastname: Wang
authors.forename: Junhang
authors.initials: J
authors.lastname: Luo
mesh_terms: D000818:Animals; D002119:Calcium Carbonate / Q000737:chemistry*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000628:therapy*
chemical_list: D053769:Nanocapsules; D034741:RNA, Small Interfering; D002119:Calcium Carbonate