Naringenin-Loaded PEGylated CuO Nanoparticles: In vitro and In silico Insights into Synergistic Therapy Against Triple Negative Breast Cancer
摘要
The major limitation of conventional targeted therapies for Triple-negative breast cancer (TNBC) is the lack of specific biomarkers. Naringenin, a natural flavonoid with potent anticancer properties, is hindered by poor aqueous solubility and low bioavailability. To enhance its therapeutic efficacy, a multifunctional nanocarrier system was developed by encapsulating naringenin into PEGylated copper oxide nanoparticles (Nar@CuONPs/PEG). The nanocomposite was synthesized via a chemical precipitation method. The UV absorbance spectra showed a surface plasmon resonance peak (SPR) at 320 nm and an indirect bandgap energy of 2.8 eV, attributed to quantum confinement effects arising from reduced particle size and dielectric modulation induced by PEG surface functionalization. FTIR confirms molecular interactions among PEG, naringenin and CuO NPs. TEM showed Nar@CuONPs/PEG with an average particle size of 13.18 ± 3.73 nm and DLS revealed the hydrodynamic size of 229.26 ± 2.6 nm, with a zeta potential of –82.8 mV. In vitro assays against MDA-MB-231 cells demonstrated enhanced cytotoxicity (IC50 = 114.84 ± 2.81 μg/mL), increased intracellular ROS production, apoptosis induction, and G0/G1 cell cycle arrest. The antibacterial activity of Nar@CuONPs/PEG at 100 μg/mL showed maximum zones of inhibition measuring 19 mm for S. aureus, 16.66 mm for E. coli, 16.33 mm for V. cholerae, and 16 mm for B. subtilis. In silico analysis identified naringenin to have moderate affinity, typical to that of flavonoids with key TNBC-related targets (SRC, ESR1, BCL2, MMP9 and ALB), and molecular dynamics simulations confirmed the structural stability of the naringenin–ESR1 complex. The strategic focus on in vitro and in silico approaches lays the basics for future translational studies, including in vivo validation.