Dr. Dae-Hwan Park1, M. Sc. Jaeyong Cho1, Dr. Oh-Joon Kwon2, Prof. Dr. Chae-Ok Yun2 and Prof. Dr. Jin-Ho Choy1,*
1 Center for Intelligent Nano-Bio Materials (CINBM), Department of Chemistry and Nano Science, Ewha Womans University, Seoul, Republic of Korea
2 Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Republic of Korea
*Corresponding author
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.
Keywords : cancer therapy; inorganic nanovectors; nanoparticles; layered compounds; siRNA delivery