BACKGROUND AND OBJECTIVESRegarding the rapid increase of antibiotic resistance and the defeat of antibiotics to treat biofilm-associated infections, it is urgent to develop new therapeutic tactics. Antimicrobial peptides (AMPs) are one of the promising molecules for fighting bacterial infections because they target bacterial membranes. Although, AMPs have some impediments hindering their further development including high manufacturing costs, low stability, and penetrability. Therefore, several types of research conducted to improve their efficacy and reduce their limitations, including the conjugation of peptides to nanoparticles. In the current work, we suggested a new core-shell formulation with a gold nanoparticle (GNP) core and a hydrophilic cationic peptide surface. We used an J۱ peptide, to establish a covalent link and concentrate the peptide on the surface of the gold nanoparticle.MATERIALS AND METHODSMethicillin-resistant Staphylococcus aureus (MRSA ATCC۴۳۳۰۰) and one clinical MRSA strain, which forms a strong biofilm, were included in this study. GNPs have been synthesized using the wet chemical route, and the conjugate was prepared by mixing different amounts of peptide aqueous solution with the gold nanoparticle solution. Synthesized samples were characterized with UV-Visible, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), Zeta potential. The minimum inhibitory concentrations (MICs) of formulations were determined by broth microdilution susceptibility test. Biofilm formation after formulations treatment was evaluated by crystal violet assay.RESULTS AND DISCUSSIONThe average sizes of GNPs were about ۶ nm. Zeta potential of GNPs showed a negative surface charge (− ۷ mV), and the conjugate was positively charged (+۷ mV). FTIR analyses indicated that the peptide successfully conjugated onto GNPs. Comparing the free peptide or GNPs alone, the conjugated variant, has three times higher antibacterial activity (MIC and MBC of conjugate = ۱۲۵ μM). The results indicated that conjugate shows improved antibiofilm activity than the peptide and GNPs (minimum biofilm inhibitory concentrations (MBIC) = ۲۵۰ μM). The enhanced antibacterial and anti-biofilm activity of the conjugated formulation could be attributed to the increased number of AMPs per NP, resulting in an improved local positive charge density, ready to break down into bacterial cells and efficiently penetrate the biofilm layer.CONCLUSIONThe current study has effectively shown that AMP conjugated NPs could be a useful approach for boosting peptide's antibacterial and antibiofilm properties.