Enhanced Delivery of Antimicrobial Peptide via Dual‐Functionalized Silica Nanoparticles Achieves Efficient <scp> <i>Staphylococcus aureus</i> </scp> Biofilm Eradication

Antimicrobial peptides (AMPs) present potential alternatives; nevertheless, their effectiveness is frequently impeded by inadequate biofilm penetration and breakdown inside the extracellular polymeric substance (EPS) matrix. This study involved the design and assessment of surface-functionalized mesoporous silica nanoparticles (MSNs) to improve the penetration and biofilm eradication efficacy of the synthetic antimicrobial and anti-biofilm peptide-276 (SAAP-276) against established Staphylococcus aureus (S. aureus) biofilms. Fluorescently labeled MSN were altered with polyethylene glycol (PEG) and polypropylene imine (PPI) to examine their penetration profiles. Confocal Raman spectroscopy investigations demonstrated that PPI-modified MSNs displayed enhanced biofilm penetration relative to PEG-modified variants, despite possessing reduced entrapment effectiveness as for PEG-PPI dual polymer conjugation. The conjugation of SAAP-276 significantly improved biofilm eradication, with TMSN-PPI-PEG-SAAP exhibiting the most efficiency due to its optimum antimicrobial peptide loading and uniform distribution throughout the biofilm matrix. Time-dependent research demonstrated that extended exposure markedly diminished biofilm viability. Our findings underscore the pivotal importance of nanoparticle surface chemistry in biofilm interactions and indicate that MSN-based AMP delivery systems can enhance biofilm eradication by enabling even and deeper penetration. These findings offer significant insights for the advancement of nanoparticle-assisted antimicrobial peptide treatments targeting persistent biofilm infections.