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<p>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&#xa0;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&#xa0;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&#xa0;°C compared to 25&#xa0;°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 (<i>BAX</i>, <i>P53</i>) and suppression of anti-apoptotic and cell cycle-regulatory genes (<i>BCL-2</i>, <i>CCND1</i>, and <i>CDK4</i>). 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.</p> Graphical Abstract <p></p>

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PEG-functionalized UiO-66 MOFs for targeted vincristine delivery: enhanced cytotoxicity in breast and ovarian cancer cell lines

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月7日

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  • Zahra Sadeghi Jam,
  • Farzaneh Tafvizi,
  • Parvin Khodarahmi,
  • Parvaneh Jafari,
  • Fahimeh Baghbani-Arani

摘要

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.

Graphical Abstract