Physiological Microenvironment Dependent Self-Cross-Linking of Multifunctional Nanohybrid for Prolonged Antibacterial Therapy via Synergistic Chemodynamic-Photothermal-Biological Processes

Herein, a multifunctional nanohybrid (PL@HPF_TM nanoparticles) was fabricated to perform the integration of chemodynamic therapy, photothermal therapy, and biological therapy over the long term at a designed location for continuous antibacterial applications. The PL@HPF_TM nanoparticles consisted of a polydopamine/hemoglobin/Fe²⁺ nanocomplex with comodification of tetrazole/alkene groups on the surface as well as coloading of antimicrobial peptides and luminol in the core. During therapy, the PL@HPF_TM nanoparticles would selectively cross-link to surrounding bacteria via tetrazole/alkene cycloaddition under chemiluminescence produced by the reaction between luminol and overexpressed H₂O₂ at the infected area. The resulting PL@HPF_TM network not only significantly damaged bacteria by Fe²⁺-catalyzed ROS production, effective photothermal conversion, and sustained release of antimicrobial peptides but dramatically enhanced the retention time of these therapeutic agents for prolonged antibacterial therapy. Both in vitro and in vivo results have shown that our PL@HPF_TM nanoparticles have much higher bactericidal efficiency and remarkably longer periods of validity than free antibacterial nanoparticles.