title: Mg(II)-Catechin nanoparticles delivering siRNA targeting EIF5A2 inhibit bladder cancer cell growth in vitro and in vivo.
abstract: Emerging evidence indicates that combination of two or more therapeutic strategies can synergistically enhance antitumor activity in cancer therapy. Here, we established a green method of generating nanocomposite particles that can be fabricated using catechin, a natural anti-cancer compound from green tea, and Mg(2+) in an easy one-step approach at room temperature. We show that Mg(II)-Catechin nanocomposite particles (Mg(II)-Cat NPs) have good biocompatibility and high cellular uptake also can load and effectively deliver small interfering RNA (siRNA) into cells in vitro and to tumor site in vivo. Mg(II)-Cat NPs by themselves had tumor-suppression effects. When complexed with siRNA that targets oncogene eukaryotic translation initiation factor 5A2 (EIF5A2), Mg(II)-Cat/siEIF5A2 complex had further enhanced anti-tumor activity. Mechanistically, we show that Mg(II)-Cat/siEIF5A2 inhibits oncogenic PI3K/Akt signal pathway. More importantly, Mg(II)-Cat/siEIF5A2 had tumor suppression effect in a clinically-relevant rat in-situ bladder cancer model. Our studies demonstrated that combination of Mg(II)-Cat NPs and siRNA is a promising therapeutic modality of combining chemotherapy with gene therapy in order to afford higher therapeutic efficacy and provided a proof of principle for such modality in a pre-clinical setting.
authors.affiliation: Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Hainan General Hospital, Haikou, 570311, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Bangfen
authors.initials: B
authors.lastname: Zhou
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.affiliation: Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Nephrology, QiLu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China. Electronic address: chenw3@mail.sysu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Departments of Internal Medicine and Molecular Biology, UT Southwestern Medical Center, Dallas, TX, 75390, USA. Electronic address: Zhi-Ping.Liu@UTsouthwestern.edu.
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Liu
authors.affiliation: Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China. Electronic address: luojunh@mail.sysu.edu.cn.
authors.forename: Junhang
authors.initials: J
authors.lastname: Luo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D019793:Fluorescein / Q000378:metabolism; D055785:Gene Knockdown Techniques; D007267:Injections; D042541:Intracellular Space / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010448:Peptide Initiation Factors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D017550:Spectroscopy, Fourier Transform Infrared; D040521:Subcutaneous Tissue / Q000473:pathology; D014018:Tissue Distribution / Q000187:drug effects; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D000970:Antineoplastic Agents; D002392:Catechin; D019793:Fluorescein; D008274:Magnesium; D010448:Peptide Initiation Factors; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A
keywords: Bladder cancer; EIF5A2; Gene therapy; Mg(II)-Catechin; Nanocomposite