Novel siRNA delivery system targeting β-catenin in colorectal cancer Cells: Synergistic effect with 5-fluorouracil
نوع المنشور
بحث أصيل
المؤلفون

Short interference RNA (siRNA) has emerged as a promising approach for the treatment of many diseases that require controlling protein expression such as cancer. Effective delivery of siRNA into cells is a challenge. This project aimed to develop a guided delivery system based on multi-walled carbon nanotubes (MWCNTs) that can deliver siRNA preferentially into colorectal cancer (CRC) cells (Caco-2) to knock down β-catenin. MWCNTs were functionalized with a tetra-amine linker to load siRNA (f-MWCNTs (8)), which was in the next stage functionalized with mannose sugar as a targeting agent (f-MWCNTs (12)). Loads of amine on f-MWCNTs (8) and f-MWCNTs (12) were 12.7 × 103 and 40 × 103 nmol/mg respectively. The amount of loaded mannose in f-MWCNTs (12) was 1.109 μg/mg. The optimum N/P ratio for loading siRNA was 5:1 for the f-MWCNTs (8) and 15:1 for the f-MWCNTs (12). siRNA-f-MWCNTs (8) knocked down β-catenin protein by about 20 % and reduced the cell viability by about 10 %, while siRNA-f-MWCNTs (12) knocked down β-catenin protein by 50 % and reduced the cell viability by 32 %. A combination of siRNA-f-MWCNTs (12) with the anticancer drug 5-fluorouracil (5-FU) reduced the cell viability by around 80 % compared to 25 % by monotherapy with 5-FU, while the combination with f-MWCNTs (8) did not show a significant effect. In conclusion, the functionalization of MWCNT with mannose increases the efficiency of siRNA delivery into Caco-2 cells and the knockdown of β-catenin can improve the sensitivity of Caco-2 cells to 5-FU.

المجلة
العنوان
Journal of Drug Delivery Science and Technology
الناشر
Elsevier
بلد الناشر
هولندا
Indexing
Thomson Reuters
معامل التأثير
4,9
نوع المنشور
Both (Printed and Online)
المجلد
110
السنة
2025
الصفحات
107082