Biodegradable Inorganic Nanovector: Passive versus Active Tumor Targeting in siRNA Transportation

Angewandte Chemie
Dae-Hwan ParkJin-Ho Choy

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.

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Citations

Apr 19, 2017·Trends in Plant Science·Wenlong BaoFrantišek Baluška
Mar 28, 2018·Nucleic Acid Therapeutics·Rahul R Nikam, Kiran R Gore
Oct 27, 2017·Macromolecular Bioscience·Peng ZhangXiqun Jiang
Feb 9, 2018·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Goeun ChoiJin-Ho Choy
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Oct 5, 2019·Nanomaterials·Wenji Jin, Dae-Hwan Park
Feb 14, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Zhongxiong FanZhenqing Hou
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Dec 12, 2016·ACS Biomaterials Science & Engineering·Xiao DuanJie Kong
Sep 9, 2019·ACS Biomaterials Science & Engineering·Chao WangXiue Jiang

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