Biocompatible Poly(acrylic acid-<i>co</i>-methacrylic acid)-Coated Iron Oxide Nanoparticles for Enhanced Adsorption and Antimicrobial Activity of Lasioglossin-III

The development of biocompatible and efficient drug delivery platforms is critical for therapeutic applications. This study investigates poly(acrylic acid-<i>co</i>-methacrylic acid)-coated iron oxide nanoparticles [ION@P(AA-<i>co</i>-MAA)] as a delivery system for the cationic antimicrobial peptide lasioglossin-III (LL-III). Iron oxide nanoparticles (IONPs) were synthesized via coprecipitation and analyzed by transmission electron microscopy, dynamic light scattering (DLS), and vibrating sample magnetometry. The coating of IONPs was performed in situ, ensuring strong polymer adhesion to the iron oxide core and functionalization with carboxy groups for peptide adsorption. The hydrodynamic diameter of polymer-coated IONPs was determined by DLS and the polymer coating was confirmed by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy through functional group signatures. ζ-Potential measurements revealed a strongly negative surface charge under physiological pH suggesting excellent colloidal stability. Investigation of LL-III adsorption on ION@P(AA-<i>co</i>-MAA) demonstrated a fast and efficient loading with 0.82 g/g at the highest investigated concentration (4 g/L LL-II), highlighting a superior adsorption efficiency compared to existing IONPs systems. After three washing steps with PBS, 49% of the peptide remained bound to the nanoparticles, indicating a stable adsorption of LL-III on the particles, markedly outperforming other IONP-based systems. The customizable polymer coating design enabled optimal peptide interactions, ensuring efficient loading and retention. Cytotoxicity studies suggested that both unloaded, and LL-III-loaded nanoparticles are biocompatible with 3T3 and HEK cells. Antimicrobial assays revealed enhanced LL-III efficacy upon nanoparticle adsorption, reducing the minimum inhibitory concentration (MIC) against <i>Escherichia coli</i> from 9.82 μM (free LL-III) to 4.59 μM for LL-III-loaded nanoparticles. These findings highlight ION@P(AA-<i>co</i>-MAA) as a promising drug delivery platform offering biocompatibility and enhanced antimicrobial efficacy laying a solid foundation for the development of advanced nanoparticle-based targeted therapies.