Jingru Xu1,2,Mengjie Gu1,2,Edward Chow2,1
National University of Singapore1,Cancer Science Institute of Singapore2
Jingru Xu1,2,Mengjie Gu1,2,Edward Chow2,1
National University of Singapore1,Cancer Science Institute of Singapore2
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and it is extremely aggressive and lethal, which commonly shows poor prognosis. Small interfering RNA (siRNA) can cause specific gene silencing. Considering that HCC is a highly heterogeneous disease which diverse oncogenes are involved in, siRNA-based gene therapy could be a potential strategy for HCC therapy. However, naked, unmodified siRNA is relatively unstable under physiological conditions and has difficulty crossing the cell membrane. Nanodiamond (ND) is carbon nanoparticle that can be used as a delivery platform. It’s highly biocompatible and well tolerated in various biological systems. Positively charged ND can bind to siRNA through electrostatic interactions. The ND-siRNA complex renders efficient cellular uptake and endosomal escape that protects siRNA from degradation.<br/>Poor penetration into solid tumors is another critical issue that limits siRNA application. Herein, we demonstrate that delivered by ND, siRNA is able to penetrate inside the tumor spheroids. The enhanced penetration capacity making ND an ideal vehicle to deliver siRNA. We further investigate the gene knockdown efficiency of siRNA targeting SALL4 delivered by ND. ND-siSALL4 can significantly knock down the SALL4 expression in tumor spheroids, which results in decreased proliferation in spheroids. Our study demonstrates the potential for ND as a promising gene delivery platform in tumor spheroids.