Influence of Yttrium (Y) Substitution in pH-Responsive 5‑Fluorouracil Delivery of Y-ZnO Nanoformulation

The rise in cancer fatalities necessitates the development of advanced treatments employing nanomaterials with better biocompatibility and efficacy. 5-Fluorouracil (5-FU), a pyrimidine analogue with potent antitumor effects, inhibits diverse solid tumors by blocking thymidylate synthase and incorporating its metabolites into RNA and DNA, preventing cancer cell proliferation. However, poor oral absorption and bioavailability limit its therapeutic efficiency. Hence, the development of a pH-stable carrier is imperative to bolster the efficacy and mitigate side effects. In this study, the synthesis of 0 to 15 wt % yttrium (Y)-doped ZnO nanostructures via the sol-gel process and the distinct characteristics from their pure counterparts have been reported. Y doping modifies the energy bandgap of ZnO, fosters oxygen vacancy formation, hinders crystal growth by reducing the energy bandgap, facilitates Y³⁺ surface segregation, and augments Y³⁺ surface enhancement. The investigation demonstrates that 10% and 15% Y-doped materials exhibit enhanced inhibitory effects on MCF-7 cancer cells relative to pure ZnO and Y-doped ZnO with 5% and 15% concentrations. With an increase in the concentration of the structure-directing doping agent, the release rate also increases, reaching a maximum after a specific duration under pH 4 conditions. The synthesized Y-doped 5-FU ZnO demonstrates precise administration of the anticancer drug at the tumor site in a stimuli-responsive, pH-dependent manner, indicating controlled release over a defined time frame. In conclusion, the findings of the reported study highlight the anticancer potential of Y-doped ZnO nanoparticles, suggesting their importance for future medicinal applications.