Light-activated nanoclusters with tunable ROS for wound infection treatment
Xin Wang, Jianing Ding, Xiao Chen, Sicheng Wang, Zhiheng Chen, Yuanyuan Chen, Guowang Zhang, Ji Liu, Tingwang Shi, Jian Song, Shihao Sheng, Guangchao Wang, Jianguang Xu, Jiacan Su, Wei Zhang, Xiaofeng Lian
Abstract
Infected wounds pose a significant clinical challenge due to bacterial resistance, recurrent infections, and impaired healing. Reactive oxygen species (ROS)-based strategies have shown promise in eradicating bacterial infections. However, the excess ROS in the infection site after treatments may cause irreversible damage to healthy tissues. To address this issue, we developed bovine serum albumin-iridium oxide nanoclusters (BSA-IrO x NCs) which enable photo-regulated ROS generation and scavenging using near infrared (NIR) laser. Upon NIR laser irradiation, BSA-IrO x NCs exhibit enhanced photodynamic therapy, destroying biofilms and killing bacteria. When the NIR laser is off, the nanoclusters' antioxidant enzyme-like activities prevent inflammation and repair damaged tissue through ROS clearance. Transcriptomic and metabolomic analyses revealed that BSA-IrO x NCs inhibit bacterial nitric oxide synthase, blocking bacterial growth and biofilm formation. Furthermore, the nanoclusters repair impaired skin by strengthening cell junctions and reducing mitochondrial damage in a fibroblast model. In vivo studies using rat infected wound models confirmed the efficacy of BSA-IrO x NCs. This study presents a promising strategy for treating biofilm-induced infected wounds by regulating the ROS microenvironment, addressing the challenges associated with current ROS-based antibacterial approaches. Schematic illustration of the main synthesis procedure of BSA-IrO x NCs, and their effect mechanisms on bacterial infection with or without the NIR laser irradiation. • 'Nanoclusters-regulating ROS' strategy for infected wound treatment. BSA-IrOx NCs uniquely control ROS via NIR laser. Integration with exogenous stimulation is effective.