Photoactivated multifunctional nanoplatform based on lysozyme-Au nanoclusters-curcumin conjugates with FRET effect and multiamplified antimicrobial activity

Photodynamic therapy is a promising alternative to antibiotics in the treatment of bacterial infection, which has the advantages of less side effects, no drug resistance and accurate treatment. However, most photosensitizers (PSs) have some disadvantages, such as poor water solubility, serious self-quenching, poor stability and so on. Therefore, solving the limitations of traditional photosensitizers has become a hot issue in photodynamic therapy. On this basis, the lysozyme (Lys)-gold nanocluster (AuNCs)-curcumin (Cur) conjugate was used as a new type of water-soluble photosensitizer and combined with the bacterial surface through electrostatic interaction to form a bacterial surface enriched in PSs. At the same time, real-time bacterial imaging can be achieved by using the fluorescence properties of Lys-AuNCs-Cur. Under 405 nm light and dark conditions, the inactivation effect of Lys-AuNCs-Cur on Staphylococcus aureus and Escherichia coli was higher than that of free Cur. Moreover, Lys-AuNCs-Cur can also produce enough ROS to kill methicillin-resistant Staphylococcus aureus. The excellent antibacterial properties of nanoparticles may be attributed to the synergism of antibacterial protein lysozyme and AuNCs-Cur nanocomplexes and the increase of 1O2 production. The results of scanning electron microscope and fluorescence microscopic imaging showed that the cell membrane of E. coli and S. aureus was seriously damaged, and facilitated penetration of Lys-AuNCs-Cur nanocomplexes into the bacteria through the damaged cell membrane, and improve the photoinactivation efficiency of bacteria. More importantly, nanoparticles exhibited almost negligible dark cytotoxicity. The coupling of Cur and gold nanoclusters can significantly improve the stability of free curcumin molecules and the ability to generate ROS. Therefore, this work is of great significance for the development of new antimicrobial agents against bacterial infection.