Synthesis, Characterization, and In Vitro Anticancer Activity of Fe3O4-PEG-Quercetin Nanoparticles in a Non-Small Cell Lung Cancer (NSCLC) Model

Objectives: Lung cancer is one of the leading causes of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for the vast majority of cases.Conventional chemotherapeutic approaches are frequently limited by systemic toxicity, poor bioavailability, and non-selective biodistribution.Nanoparticle-based drug delivery systems have emerged as a promising strategy to overcome these limitations.The present study aimed to synthesize a novel PEGylated magnetite nanoparticle system containing quercetin (Fe 3 O 4 -PEG-QUER) and evaluate its effects on the impedance-based cellular responses of the A549 NSCLC cell line compared with non-tumorigenic bronchial epithelial cells (BEAS-2B).Materials and Methods: Nanoparticles were synthesized via the coprecipitation method.Quercetin was introduced during the preparation of the Fe 3 O 4 -PEG formulation, resulting in the Fe 3 O 4 -PEG-QUER formulation.All formulations Fe 3 O 4 , Fe 3 O 4 -QUER, Fe 3 O 4 -PEG, and Fe 3 O 4 -PEG-QUER were characterized using X-ray diffraction, fourier-transform infrared spectroscopy, Zeta-sizer, and nanoparticle tracking analysis.Impedance-based cellular responses were assessed in BEAS-2B and A549 cell lines using the xCELLigence real-time cell analysis system.Results: Fe 3 O 4 -PEG-QUER showed apparent antiproliferative effects against A549 cells, with IC50 values of 289 µg/mL at 24 h and 160 µg/mL at 48 h.For BEAS-2B cells, the apparent IC50 values were above the highest tested concentration (> 400 µg/mL) at the evaluated time points.Fe 3 O 4 -PEG alone showed marked effects on the impedance-based cellular response of A549 cells, with apparent IC50 values of 27 and 19 µg/ mL at 24 and 48 h, respectively.Because quercetin loading was not quantitatively determined, the nanoparticle concentrations represent total formulation mass and cannot be directly converted to quercetin-equivalent doses.Conclusion: Fe 3 O 4 -PEG-QUER nanoparticles altered the impedance-based cellular response in the A549 NSCLC cell line, with smaller changes observed in BEAS-2B cells at lower concentrations.These findings provide preliminary in vitro evidence supporting further investigation of Fe 3 O 4 -PEG-QUER in lung cancer models.