title: Biodegradable Inorganic Nanovector: Passive versus Active Tumor Targeting in siRNA Transportation.
abstract: The biodegradable inorganic nanovector based on a layered double hydroxide (LDH) holds great promise for gene and drug delivery systems. However, in vivo targeted delivery of genes through LDH still remains a key challenge in the development of RNA interference therapeutics. Here, we describe in vivo and in vitro delivery system for Survivin siRNA (siSurvivin) assembled with passive LDH with a particle size of 100 nm or active LDH conjugated with a cancer overexpressing receptor targeting ligand, folic acid (LDHFA), conferring them an ability to target the tumor by either EPR-based clathrin-mediated or folate receptor-mediated endocytosis. When not only transfected into KB cells but also injected into xenograft mice, LDHFA/siSurvivin induced potent gene silencing at mRNA and protein levels in vitro, and consequently achieved a 3.0-fold higher suppression of tumor volume than LDH/siSurvivin in vivo. This anti-tumor effect was attributed to a selectively 1.2-fold higher accumulation of siSurvivin in tumor tissue compared with other organs. Targeting to the tumor with inorganic nanovector can guide and accelerate an evolution of next-generation theranosis system.
authors.affiliation: Center for Intelligent Nano-Bio Materials (CINBM), Department of Chemistry and Nano Science, Ewha Womans University, Seoul, 120-750, Republic of Korea.
authors.forename: Dae-Hwan
authors.initials: DH
authors.lastname: Park
authors.affiliation: Center for Intelligent Nano-Bio Materials (CINBM), Department of Chemistry and Nano Science, Ewha Womans University, Seoul, 120-750, Republic of Korea.
authors.forename: Jaeyong
authors.initials: J
authors.lastname: Cho
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul, 133-791, Republic of Korea.
authors.forename: Oh-Joon
authors.initials: OJ
authors.lastname: Kwon
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul, 133-791, Republic of Korea.
authors.forename: Chae-Ok
authors.initials: CO
authors.lastname: Yun
authors.affiliation: Center for Intelligent Nano-Bio Materials (CINBM), Department of Chemistry and Nano Science, Ewha Womans University, Seoul, 120-750, Republic of Korea. jhchoy@ewha.ac.kr.
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Choy
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D005822:Genetic Vectors; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008855:Microscopy, Electron, Scanning; D049329:Nanostructures; D009369:Neoplasms / Q000628:therapy*; D034741:RNA, Small Interfering / Q000378:metabolism*
chemical_list: D001672:Biocompatible Materials; D034741:RNA, Small Interfering; D007770:L-Lactate Dehydrogenase
keywords: cancer therapy; inorganic nanovectors; layered compounds; nanoparticles; siRNA delivery