Magnetic silk fibroin nanospheres loaded with amphiphilic polypeptides and antibiotics for biofilm eradication

The eradication of established biofilms is a highly challenging task, due to the protective barrier effect of extracellular polymeric substances (EPS) and the presence of persister cells. Both increased drug permeability and elimination of persister cells are essential for the eradication of biofilms. Here, magnetic silk fibroin nanospheres loaded with antibiotics and host defense peptide (HDP) mimics (MPSN/S@P) were developed to demonstrate a new strategy for biofilm eradication. As an HDP mimic, an amphiphilic polypeptide containing 90% L-lysine and 10% L-valine (Lys₉₀Val₁₀) was selected for loading onto magnetic silk fibroin nanospheres via electrostatic interactions. Lys₉₀Val₁₀ exhibited excellent antibacterial activities against both planktonic and persister cells of Staphylococcus aureus (S. aureus). As a representative of the hydrophobic drug, spiramycin (SPM) was conveniently embedded into the β-sheet domain during the self-assembly process of silk fibroin. The sustained release of SPM during biofilm eradication enhanced the antibacterial efficacy of MPSN/S@P. The antibacterial test demonstrated that the extract from the MPSN/S@P suspension can kill both planktonic and persister cells of S. aureus, as well as inhibiting biofilm formation. Importantly, with the assistance of magnetic guidance and photothermal effects derived from Fe₃O₄ nanoparticles (Fe₃O₄ NPs), over 92% of bacteria in the biofilm were killed by MPSN/S@P, indicating the successful eradication of mature biofilms. The simple preparation method, integration of photothermal and magnetic responsiveness, and persister cell killing functions of MPSN/S@P provide an accessible strategy and illustrative paradigm for efficient biofilm eradication.