PEG-functionalized UiO-66 MOFs for targeted vincristine delivery: enhanced cytotoxicity in breast and ovarian cancer cell lines
Zahra Sadeghi Jam, Farzaneh Tafvizi, Parvin Khodarahmi, Parvaneh Jafari, Fahimeh Baghbani‐Arani
Abstract
Vincristine (VIN) inhibits microtubule formation in the mitotic spindle, effectively arresting cells in mitosis. This study aimed to develop a polyethylene glycol (PEG)-functionalized UiO-66 metal–organic framework (MOF) as a targeted drug delivery system for VIN in MDA-MB-231 (breast cancer) and A2780 (ovarian cancer) cell lines. The synthesized UiO-66–VIN–PEG nanoparticles exhibited a mean diameter of 223.5 ± 7.45 nm with a spherical morphology. Fourier transform infrared spectroscopy (FT-IR) confirmed successful VIN loading onto the UiO-66 structure. Drug release studies demonstrated a gradual, pH-dependent release profile, with VIN release reaching 55% at pH 7.4 and 75% at pH 5.4 over 72 h, highlighting the system's responsiveness to the acidic tumor microenvironment. Stability assessments indicated that size, polydispersity index (PDI), and entrapment efficiency (EE%) remained more stable at 4 °C compared to 25 °C. In vitro experiments demonstrated significant cytotoxicity and apoptosis induction in MDA-MB-231 and A2780 cells. This was evidenced by increased expression of pro-apoptotic genes (BAX, P53) and suppression of anti-apoptotic and cell cycle-regulatory genes (BCL-2, CCND1, and CDK4). In addition, a notable elevation in DCF fluorescence was observed in UiO-66–VIN-treated and UiO-66–VIN–PEG-treated cells compared to controls. These findings underscore the potential of UiO-66–VIN–PEG as a pH-responsive, targeted drug delivery platform for enhancing VIN's anti-cancer efficacy in breast and ovarian cancer.