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

Abstract

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 <i>in vitro</i> and <i>in vivo</i> results have shown that our PL@HPF_TM nanoparticles have much higher bactericidal efficiency and remarkably longer periods of validity than free antibacterial nanoparticles.