Antimicrobial Peptide-Loaded Mesoporous Silica Nanoparticles: A pH-Triggered Controlled Release against Biofilms

The rapid emergence of multidrug-resistant bacteria has intensified interest in antimicrobial peptides (AMPs) as alternative therapeutics due to their potent broad-spectrum activity and low propensity for inducing resistance. However, the clinical translation of AMPs is hindered by their inherent low stability and susceptibility to proteolytic degradation. In this study, we investigated a pH-responsive delivery system using mesoporous silica nanoparticles (MSNs) to encapsulate frog-derived temporin B and scorpion-derived BmKn2two AMPs that have shown particular promiseaiming to enhance their stability and enable targeted eradication of <i>Staphylococcus aureus</i> biofilms. AMPs were efficiently adsorbed onto MSNs via electrostatic interactions, achieving a high loading capacity. The release of peptides was minimal at physiological pH (7.4) but was significantly accelerated under mildly acidic conditions (pH 5.5), typical of biofilm environments. This tunable release behavior enabled controlled delivery and improved protection of the peptides from enzymatic degradation. In vitro studies demonstrated that AMP-loaded MSNs retained antibacterial and antibiofilm activity against <i>Staphylococcus aureus</i>, comparable to that of free peptides, while offering stability. The adaptability of this MSN-based platform to other AMPs with similar physicochemical properties highlights its broader potential for combating resistant bacterial infections.