One of the newest strategies in cancer therapy; is the utilization of siRNA to control gene expression. However, effective delivery of siRNA into cells is a challenge, particularly in vivo. To deliver these types of molecules without causing significant harm, researchers are developing new technological delivery systems. The development of drug delivery systems based on carbon nanotubes has received a lot of attention in this respect. Our project aims to develop a new method for delivering siRNA into colon cancer cells in order to target the expression of the β-catenin protein, which plays a role in a variety of developmental processes; such as cell growth and proliferation, embryonic patterning, cell differentiation, and other cellular functions. The new approach is based on the synthesis of a new nano-system of MWCNTs functionalized with a tetra-amine linker and mannose sugar as a targeting agent to increase the nano-system`s uptake and selectivity. We successfully functionalized MWCNTs with tetra-amine groups, which were then functionalized with mannose molecules. The amount of the mannose and amine attached groups were also quantified. The N/P ratio required to trap β-catenin siRNA was determined by agarose gel. Western blot analysis revealed that our compound significantly reduced β-catenin protein expression (p > 0.05). The knockdown percentage was 50% of f-MWCNTs. We hypothesized that the possible up-regulation of mannose receptors on the surface of caco-2 cells may increase the transfection efficacy of f-MWCNTs. The MTS results showed that the down-regulation of β-catenin protein can restrict cancer cell growth and prevent cell proliferation which was shown significantly in both transfection approaches with an IC50 equal to 19.32 μg/ml for f-MWCNT-siRNA. Also, this effect can increase the efficacy of 5-FU in colon cancer significantly compared with control. Therefore, we propose that our approach could be implemented in the setting of colon cancer therapy.

Conference Title

International Conference on General Health Sciences

Conference Country

Palestine

Conference Date

May 2, 2024 - May 5, 2024

Conference Sponsor

Gaziantep university