Silver–PEG Nanoparticle–Based Encapsulation of 5‐Fluorouracil for Enhanced Anticancer Efficacy and Controlled Drug Delivery

Cancer therapy requires drug delivery systems that enhance efficacy while minimizing systemic toxicity. This study aimed to develop a multifunctional, biocompatible nanocarrier for 5‐fluorouracil (5‐FU) with pH‐responsive release and complementary biological activity. Silver nanoparticles (AgNPs) were biosynthesized using Ocimum sanctum leaf extract, functionalized with polyethylene glycol (PEG), and subsequently loaded with 5‐FU to form Ag@PEG‐5‐FU‐NPs. The structural, morphological, and thermal characteristics of the nanocarrier were confirmed by UV–Vis, FTIR, SEM, HRTEM, XRD, and TGA analyses. In vitro assays including pH‐dependent drug release, human red blood cell (HRBC) membrane stabilization, and cytotoxicity studies on A549, MDA‐MB‐231, and MCF‐7 cell lines were used to evaluate therapeutic performance. The Ag@PEG‐5‐FU‐NPs exhibited pronounced pH‐responsive behavior, with cumulative 5‐FU release reaching 84.10 ± 5.20% at pH 5.2 compared to 63.56 ± 1.25% at pH 7.4. The system also demonstrated strong anti‐inflammatory activity (IC 50 = 22.15 µg/mL) and potent anticancer effects, especially against A549 lung cancer cells (IC 50 = 11.15 µg/mL). Overall, the results highlight Ag@PEG‐5‐FU‐NPs as a promising, multifunctional nanotherapeutic platform for efficient cancer treatment.