Engineered zein-casein sodium nanoparticles enhance quinoline delivery for selective ovarian cancer cell apoptosis and oxidative stress modulation; an in vitro and in silico study

Quinoline derivatives possess anticancer potential but are limited by poor solubility and specificity. Nanoparticle-based delivery systems, such as zein–casein sodium nanoparticles (ZCNPs), offer improved stability, bioavailability, and tumor targeting. Quinoline was profiled using SwissADME and docked (Molecular Operating Environment (MOE)) against Polypyrimidine Tract Binding protein (PTB) (2 AD9) and Fibroblast Growth Factor 2 (FGF2) (1EV2). QZCNPs were synthesized via antisolvent precipitation, characterized by Dynamic Light Scattering (DLS) ( Z -average 157.13 ± 4.6 nm, Polydispersity Index (PDI) 0.279 ± 0.034), Field Emission Scanning Electron Microscopy (FESEM) (151 ± 7 nm), Fourier Transform Infrared Spectroscopy (FTIR), and zeta potential (−38.49 ± 1.49 mV). Ultraviolet-Visible Spectroscopy (UV–Vis) determined encapsulation efficiency at 320 nm. In vitro evaluation included MTT assays on A2780 cancer and Human Dermal Fibroblasts (HDF) normal cells, apoptosis analysis (flow cytometry, Acridine Orange/Propidium Iodide (AO/PI)), qRT-PCR (Nuclear Factor kappa B (NFκB), Tumor Necrosis Factor-alpha (TNF-α), Matrix Metalloproteinase-2 (MMP2); Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH)-normalized), and antioxidant assays (ABTS + /DPPH). In silico analysis confirmed favorable drug-likeness and Gastrointestinal (GI) absorption. Docking revealed optimal PTB binding (S-score − 4.69) via SER131 hydrogen bond and HIS62 hydrophobic contacts. Zein/casein affinities exceeded cancer targets, yielding 84.31% encapsulation. QZCNPs showed sustained release (12% burst at 2 h, 82% at 96 h). Cytotoxicity was dose-dependent in A2780 cells (IC₅₀ ≈ 125 μg/mL) with 61.48 ± 0.53% viability at 125 μg/mL and 42.34 ± 3.94% at 500 μg/mL, while HDF cells tolerated 250 μg/mL (94.37 ± 3.00% viability). Apoptosis increased from 0.84 ± 0.15% (control) to 54.7 ± 4.3% at 412 μg/mL ( p < 0.001). Gene expression at 412 μg/mL revealed NFκB suppression (0.41 ± 0.05, p < 0.01), TNF-α reduction (0.51 ± 0.04, p < 0.01), and MMP2 downregulation (0.55 ± 0.07, p < 0.05). Antioxidant activity achieved complete ABTS + inhibition at 1000 μg/mL (Trolox Equivalents (TE) 185.8 ± 9.2 μg/mL), outperforming empty nanoparticles (1.14 ± 0.05 vs 0.21 ± 0.03 mmol Trolox/g, p < 0.001). QZCNPs selectively induce ovarian cancer apoptosis, suppress pro-tumorigenic genes, and exert potent antioxidant effects, overcoming quinoline's delivery limitations. This multifunctional platform warrants in vivo validation. • Hybrid zein-casein nanoparticles (157 nm, −38.5 mV zeta) achieve 84.3% quinoline encapsulation for tumor targeting. • Selective A2780 cell apoptosis (54.7%) via NFκB/MMP2 suppression & reduced oxidative stress by QZCNPs. • Dual ABTS + /DPPH radical scavenging (100%) enhances anticancer therapy by mitigating oxidative damage.