Nano-drug codelivery system of vincristine and gemcitabine loaded hyaluronan-altered hollow mesoporous silica nanoparticles: investigation of in vitro drug release and anticancer activity in pancreatic cancer cells.

This study involves the co-loading of Vincristine (VC) and Gemcitabine (GT), two anticancer compounds, into hollow mesoporous silica nanoparticles (HA-SS-HMS) to specifically target pancreatic cancer cells, utilizing targeting and capping agent of hyaluronic acid (HA) and redox-sensitive linkers of S-S bonds. Well-dispersed HA-SS-HMS are fabricated with a diameter of less than 150 nm. Comprehensive chemical-physical characterization of the fabricated HA-SS-HMS utilized FTIR, FE-SEM, TEM, DLS, TGA, and BET techniques. The drug release experiment demonstrated regulated and pH-responsive behavior in the presence of HAase and GSH at pH levels 5.0 and 7.4. The targeting capability and dispersion of VC/GT@HA-SS-HMS in CD44(+) PANC- 1 pancreatic cancer cells were evidenced by fluorescence microscopic imaging. Furthermore, VC/GT@HA-SS-HMS demonstrated superior synergistic cytotoxicity and apoptotic rates relative to VC or GT-loaded HA-SS-HMS and the free VC/GT combination against the PANC- 1 cell line. The biochemical staining outcomes indicated a significant change in apoptosis ratio in cells treated with VC/GT@HA-SS-HMS. Collectively, our research demonstrates the promise of HA-SS-HMS as an effective nanoparticle-based approach for targeted and induced codelivery of VC/GT combination in the treatment of pancreatic cancer cells.