Alternative Copper-Based Single-Atom Nanozyme with Superior Multienzyme Activities and NIR-II Responsiveness to Fight against Deep Tissue Infections
Jiaxiang Bai, Yonghai Feng, Wenming Li, Zerui Cheng, Jessica M. Rosenholm, Huilin Yang, Guoqing Pan, Hongbo Zhang, Dechun Geng
Abstract
Nanozymes are considered to represent a new era of antibacterial agents, while their antibacterial efficiency is limited by the increasing tissue depth of infection. To address this issue, here, we report a copper and silk fibroin (Cu-SF) complex strategy to synthesize alternative copper single-atom nanozymes (SAzymes) with atomically dispersed copper sites anchored on ultrathin 2D porous N-doped carbon nanosheets (CuN x -CNS) and tunable N coordination numbers in the CuN x sites ( x = 2 or 4). The CuN x -CNS SAzymes inherently possess triple peroxidase (POD)-, catalase (CAT)-, and oxidase (OXD)-like activities, facilitating the conversion of H 2 O 2 and O 2 into reactive oxygen species (ROS) through parallel POD- and OXD-like or cascaded CAT- and OXD-like reactions. Compared to CuN 2 -CNS, tailoring the N coordination number from 2 to 4 endows the SAzyme (CuN 4 -CNS) with higher multienzyme activities due to its superior electron structure and lower energy barrier. Meanwhile, CuN x -CNS display strong absorption in the second near-infrared (NIR-II) biowindow with deeper tissue penetration, offering NIR-II-responsive enhanced ROS generation and photothermal treatment in deep tissues. The in vitro and in vivo results demonstrate that the optimal CuN 4 -CNS can effectively inhibit multidrug-resistant bacteria and eliminate stubborn biofilms, thus exhibiting high therapeutic efficacy in both superficial skin wound and deep implant-related biofilm infections.