Persistent Production of Reactive Oxygen Species with Zn₂GeO₄:Cu Nanorod-Loaded Microneedles for Methicillin-Resistant Staphylococcus Aureus Infectious Wound Healing

Skin wound infection caused by methicillin-resistant Staphylococcus aureus (MRSA) is an urgent concern. Photodynamic therapy has emerged as a promising means of combating bacterial infection. However, continuous or repeated in situ light excitation is required for photosensitizers to produce reactive oxygen species (ROS), and most photosensitizers need sufficient oxygen to produce singlet oxygen (1O2), which greatly limits their clinical application. In this work, we report the preparation of Zn2GeO4:Cu2+ (ZGC) persistent luminescence nanorods with excellent ability for persistent ROS production after stopping excitation for MRSA infectious wound healing. The prepared ZGC nanorods were loaded into dissolvable microneedles (MNs) (ZGC@MNs) to penetrate biofilms and treat MRSA-infected wounds in a minimally invasive manner. ZGC showed a long-persistent photocatalytic effect to constantly produce multiple ROS (1O2, hydroxyl radical, and superoxide radical) accompanied by persistent luminescence after a pre-illumination. The MN tips of ZGC@MNs were rapidly dissolved to release ZGC for the continuous production of multiple ROS for at least 48 h with no need for in situ excitation and no special requirement on the amount of oxygen for eliminating MRSA biofilms. The developed ZGC@MN patches exhibited excellent antibacterial activity and biocompatibility for effectively reducing inflammation and promoting wound healing in vivo.