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

Abstract

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 ( 1 O 2 ), which greatly limits their clinical application. In this work, we report the preparation of Zn 2 GeO 4 :Cu 2+ (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 longpersistent photocatalytic effect to constantly produce multiple ROS ( 1 O 2 , 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.

Microneedles for in situ tissue regeneration

“…For example, Yan et al. incorporated the photosensitizer Zn 2 GeO 4 :Cu 2+ (ZGC) into dissolving MNs [ 108 ]. The prepared MNs penetrated biofilms in a minimally invasive manner and delivered pre-UV-treated ZGC to infected wounds.…”

Breaching Bacterial Biofilm Barriers: Efficient Combinatorial Theranostics for Multidrug-Resistant Bacterial Biofilms with a Novel Penetration-Enhanced AIEgen Probe

“…Antibacterial agents involve antibiotics, natural extracts, cationic polymers, antimicrobial peptides, , and antibacterial materials. − Most of them are not able to pass through the biofilm barriers efficiently, thus limiting their efficacies in the therapy of biofilm-associated infection. Mature biofilms act as barriers to antimicrobial agents by restricting their diffusion and preventing them from penetrating deeply into the matrix. − Thus, novel therapeutic agents and strategies capable of fully accessing inside bacteria by penetrating the biofilm barriers for tackling biofilms are urgently needed . It was reported that molecules carrying positive charges would demonstrate comparably stronger biofilm penetration than neutral or negatively charged molecules. − Wang and co-workers designed a guanidinium-functionalized pillar arene with a high antibacterial efficacy to disrupt biofilms .…”

“…33−35 Thus, novel therapeutic agents and strategies capable of fully accessing inside bacteria by penetrating the biofilm barriers for tackling biofilms are urgently needed. 36 was reported that molecules carrying positive charges would demonstrate comparably stronger biofilm penetration than neutral or negatively charged molecules. 37−40 Wang and coworkers designed a guanidinium-functionalized pillar 5 arene with a high antibacterial efficacy to disrupt biofilms.…”

Interfacial Regulation of ZIF-67 on Bacteria to Generate Bifunctional Sensing Material on Chip for Qualifying Cell-Released Reactive Oxygen Species

“…Different methods such as fluorescence, luminescence, and electrochemical methods have been developed for ROS detection. Among them, electrochemical methods exhibit advantages including good sensitivity, reliable reproducibility, short response time, and easy miniaturization .…”