Engineered exosome hybrid copper nanoscale antibiotics facilitate simultaneous self-assembly imaging and elimination of intracellular multidrug-resistant superbugs

With the increasing emergence of bacterial infections, especially multidrug-resistant (MDR) bacteria, poses an urgent threat. This study demonstrated a novel multifunctional nanotheranostics platform developed by the strategic integration of both in-situ bio-assembly imaging and target bacteria inactivation. Through the introduction of copper ions into bacteria, the Cu²⁺ could spontaneously bio-self-assembled into a multifunctional copper nanoclusters (NCs) which efficiently enhanced epigallocatechin gallate (EGCG) uptake into bacteria. While visualizing the bacteria, the developed theranostic nanoplatform exhibited highly efficient disinfection activities with negligible side effects as reflected by higher cell viability and insignificant hemolytic effects. Furthermore, the exosomal formulation of EGCG integrated with Cu²⁺ showed an increased intracellular antibacterial activity, which could eliminate most of the methicillin-resistant Staphylococcus aureus (MRSA) phagocytosed by macrophages, guide macrophages toward M2-like phenotype polarization and alleviate inflammation, without exhibiting obvious cytotoxicity on host RAW264.7. The regimen could be viewed as an effective strategy for the sterilization of intractable bacterial infections.