Cell Growth Inhibition Effect of DsiRNA Vectorised by Pectin-Coated Chitosan-Graphene Oxide Nanocomposites as Potential Therapy for Colon Cancer

Abstract

Colonic-Targeted drug delivery system is widely explored to combat colon-related diseases such as colon cancer. Dicer-substrate small interfering RNA (DsiRNA) has been explored for cancer therapy due to its potency in targeting specific gene of interest. However, its application is limited by rapid degradation and poor cellular uptake. To address this, chitosan-graphene oxide (CS-GO) nanocomposite was used to deliver DsiRNA effectively into cells. Additionally, pectin was used as compatibilization agent to allow specific delivery to the colon and protect the nanocomposites from the harsh environment in the stomach and small intestine. CS-GO-DsiRNA nanocomposites were prepared by electrostatic interaction between CS and GO prior to coating with pectin. The mean particle size of CS-GO-DsiRNA-pectin nanocomposites was 554.5±124.6 nm with PDI and zeta potential of 0.47±0.19 and-10.7±3.0 mV, respectively. TEM analysis revealed smooth and spherical shape of CS-GO-DsiRNA nanocomposites and the shape became irregular after pectin coating. FTIR analysis further confirmed the successful formation of CS-GO-DsiRNA-pectin nanocomposites. Furthermore, the nanocomposites were able to entrap high amount of DsiRNA (% entrapment efficiency of 92.6±3.9%) with strong binding efficiency. CS-GO-DsiRNA-pectin nanocomposites also selectively inhibited cell growth of colon cancer cell line (Caco-2 cells) and were able to decrease VEGF level significantly. In a nutshell, pectin-coated DsiRNA-loaded CS-GO nanocomposites were successfully developed and they have a great potential to deliver DsiRNA to the colon effectively.