Design of Peptide-Modified Aluminum Nanoparticles with Enhanced Antimicrobial, Antibiofilm, Antioxidant, and DNA-Cleaving Properties

<b>Background/Objectives</b>: In this study, three antimicrobial peptides (<b>1</b>-<b>3</b>) were conjugated onto bare aluminum nanoparticles (<b>NP</b>) to produce peptide-conjugated nanoparticles (<b>NP1</b>-<b>NP3</b>) in order to evaluate their biological effects. <b>Methods</b>: The peptide-functionalized Al₂O₃ nanoparticles were characterized and subsequently analyzed for their antimicrobial activity against selected bacterial strains. The findings were compared with those of bare Al₂O₃ nanoparticles and free antimicrobial peptides. Through this comparison, the enhanced impact of combining nanoparticles with peptides in addressing antimicrobial resistance was demonstrated. Additionally, biofilm inhibition, microbial cell viability inhibition, DNA cleavage, antioxidant, and amylolytic activity assays were performed to comprehensively evaluate the biological functionality of the synthesized nanoparticles. <b>Results</b>: Although all tested samples exhibited significant antimicrobial activity, peptide-conjugated nanoparticles <b>NP1</b>, <b>NP2</b>, and <b>NP3</b> provided superior activity with an MIC value of 16 mg/L. The highest biofilm inhibition activities were observed for <b>NP2</b> as 53% and 70% against <i>S. aureus</i> and <i>P. aeruginosa</i>, respectively. Additionally, <b>NP1</b>-<b>NP3</b> inhibited microbial cell viability by 100% at a concentration of 6.25 mg/L and free peptide <b>3</b> displayed <i>E. coli</i> inhibition as 100% at a concentration of 12.5 mg/L. Furthermore, we evaluated the biological potential of antimicrobial peptide-functionalized Al₂O₃ nanoparticles through antibiofilm, antioxidant, antidiabetic activities, and DNA cleavage assays. Peptide-conjugated nanoparticles <b>NP1</b>, <b>NP2</b>, and <b>NP3</b> exhibited the highest antioxidant activities as 43.70%, 45.22%, and 59.57%, respectively. Except for <b>NP3</b>, the compounds were observed to act as α-amylase enzyme activators. <b>NP</b> and <b>NP1</b>-<b>NP3</b> completely degraded the supercoiled circular form into small pieces. <b>Conclusions</b>: Our findings suggest that peptide-aluminum nanoparticle conjugation may be a promising formulation for enhancing biological activity. Further in vitro and in vivo tests may help clarify the therapeutic potential of this novel nanoformulation.