Design and Development of Teixobactin Analog-Loaded Magnetic Nanocomposites for Biofilm Destruction and Pathogen Elimination

Although teixobactin, a promising cyclic undecadepsipeptide, exhibits efficacy against Gram-positive bacteria due to its novel mode of action and low potential for resistance, its clinical application is limited by two key shortcomings: ineffectiveness against Gram-negative bacteria and poor penetration of the protective extracellular polymeric substance (EPS) in biofilms. This renders it unsuitable for targeting the polymicrobial biofilms, which are the cause of periodontitis and peri-implantitis. We designed a modified teixobactin analog by integrating rhamnolipid, Ag@Fe3O4 nanoparticles, and L-Chg10-teixobactin to obtain a novel magnetic nanoparticle (MNP). The MNP demonstrates the ability to simultaneously degrade EPS, penetrate biofilm structures, and eliminate both G+ and G- pathogens under a rotating magnetic field (RMF). Rhamnolipid grafting degraded 52.5% of biofilm EPS. MNPs showed broad-spectrum antimicrobial activity, with minimal inhibitory concentrations from 100 to 200 µg/mL. Combined with RMF, biofilm eradication rates reached 97.0% (E. faecalis), 97.7% (S. gordonii), 88.4% (P. gingivalis), and 74.2% (F. nucleatum). The biofilm thickness was reduced from 19.4 ± 2.9 µm to 7.4 ± 1.0 µm, and the biofilm biomass was reduced by 68.5%. This combined strategy integrates enzymatic EPS degradation, magneto-mechanical disruption, and dual antimicrobial action, offering a promising topical therapy for periodontitis and peri-implantitis.