Investigation of the cytotoxic and antimetastatic effect of metformin loaded silica nanoparticles on pancreatic cancer cell line

Pancreatic cancer is characterized by its aggressive behavior, resistance to treatment, and short survival rate. Innovative technologies that enhance conventional treatments are being investigated to fight this condition globally. Nanotechnology is among these emerging technologies. Nanotechnology in nanomedicine has garnered interest for its medication delivery techniques. Metformin is a diabetes medication that has demonstrated efficacy in several cancer cells in recent years. This thesis aimed to investigate the cytotoxic and antimetastatic effects of the controlled release of metformin hydrochloride (MET), the active component of metformin, by loading it into porous silica nanoparticles synthesized via the microemulsion method on pancreatic cancer (PANC-1) cell lines. Porous silica nanoparticles (GSNP) generated via the microemulsion technique were characterized using FE-SEM, FT-IR, BET, and XRD analyses. The loading efficiency and release of GSNP were determined by measuring absorbance at 233 nm using a UV-Vis spectrophotometer. The cytotoxic effects of MET, GSNP, and Metformin hydrochloride-loaded GSNP (GSNP+MET) on PANC-1 cancer cells were assessed using the MTT assay at three different time periods (24-48-72 hours). The antimetastasis impact was concurrently examined using the Wound Healing technique. The MTT analysis results for MET, GSNP, and GSNP+MET yielded IC50 values of 95.9146 mM, 12.230 mM, and 10.391 mM for 24 hours; 37.769 mM, 18.003 mM, and 14.194 mM for 48 hours; and 27.124 mM, 13.708 mM, and 11.786 mM for 72 hours, respectively. The results indicate that GSNP+MET exhibit more cytotoxicity against. Based on these results, the application of GSNP+MET showed approximately 89%, 62%, and 56% more cytotoxicity on PANC-1 cell at 24, 48, and 72 hours, respectively compared to MET alone. Additionally, compared to GSNP alone, it exhibited approximately 15%, 21%, and 14% higher cytotoxic effect at the same time points. The most effective amount of GSNP+MET was determined to be 10.391 mM at the 24-hour period. Based on this effective IC50 concentration, the concentration of all three applications was adjusted to 10 mM and the antimetastasis effect in the PANC-1 cell line was determined by migration assay. The migration investigation revealed that after 0-24 hours, the negative control entirely closed the wound area, whereas MET achieved 84% closure, GSNP 39%, and GSNP+MET 33%. It was concluded that GSNP+MET had a superior antimetastatic effect relative to GSNP and MET. Consequently, the GSNP+MET complex has been found to possess novel therapeutic potential beyond conventional therapies for pancreatic cancer. Porous silica nanoparticles represent a promising alternative carrier for effective drug delivery systems by targeting and biomarkers.