In vitro evaluation of hyaluronate-functionalized multi-walled carbon nanotubes containing trigonelline for their anti-cancer activity on A2780 ovarian cancer cells
摘要
Ovarian cancer is a significant cause of gynecological cancer deaths globally, with current treatments having limited effectiveness and notable side effects. Nanocarrier-based targeted drug delivery systems present a promising strategy to enhance treatment outcomes. This study investigates the cytotoxic effects of multi-walled carbon nanotube-hyaluronic acid-trigonelline (MWCNT-HA-TG) nanocarriers (NCs) on the human ovarian cancer cell line A2780 for the first time. The dynamic light scattering (DLS) analysis revealed a Z-average particle size of 121.7 nm with a polydispersity index (PDI) of 0.2990, indicating moderate size heterogeneity. The zeta potential was measured at -25.46 ± 11.24 mV, suggesting a moderately stable colloidal system. Scanning electron microscopy (SEM) demonstrated a highly interconnected network of MWCNTs within the matrix. Fourier-transform infrared (FTIR) spectroscopy identified characteristic peaks for carboxyl, carbonyl, and hydroxyl groups, validating the successful incorporation of HA and TG. The encapsulation efficiency of TG in the NCs was determined to be 88.45% and the cumulative drug release exhibited an initial burst of 15.4% within 3 h, reaching 84.2% by 72 h. The MTT assay’s cytotoxicity assessment revealed a concentration-dependent decrease in A2780 cell viability, with an IC50 of 36.11 µg/mL. In contrast, HDF cells showed significantly lower sensitivity (IC50 > 500 µg/mL). Flow cytometry analysis revealed an increase in apoptotic populations in A2780 cells, with significant increases in both early and late apoptosis as the concentration rose from 3.6 µg/mL to 136 µg/mL. Real-time PCR results demonstrated upregulation of caspase-8, caspase-9, and P53 expressions in TG-treated A2780 cells, indicating a concentration-dependent induction of apoptosis. These findings suggest that MWCNT-HA-TG NCs possess selective cytotoxicity against ovarian cancer cells, presenting a promising strategy for targeted cancer therapy.