Alternative Copper-Based Single-Atom Nanozyme with Superior Multienzyme Activities and NIR-II Responsiveness to Fight against Deep Tissue Infections

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.

Single atom nanozymes for bacterial infection therapy

“…Previous studies have demonstrated that the catalytic activity of a Cu-based single atom catalyst depends on the N coordination number of the Cu atom. 50 More recently, Bai et al 51 developed Cu-based SAzymes with an adjustable N coordination number by pyrolyzing Cu–silk fibroin complexes. The authors found that CuN x –CNS SAzymes with a CuN 4 structure exhibited superior multienzyme activity (POD-, OXD- and CAT-like) than those with a CuN 2 structure.…”

CaO2–Cu2O micromotors accelerate infected wound healing through antibacterial functions, hemostasis, improved cell migration, and inflammatory regulation

“…Presently, for the treatment of deep wounds, numerous recently developed antibacterial particles, including nanoenzymes and a combination of photothermal therapy and simulated enzyme catalysis, exhibit outstanding antibacterial effectiveness and tissue repair capabilities. [18][19][20] In contrast to certain metallic or precious metal nanoenzymes, the preparation process for CaO 2 -Cu 2 O does not necessitate any specialized equipment, resulting in lower costs while still achieving desirable therapeutic effects.…”

Near-Infrared-II-Driven Pollen Micromotors for Inflammatory Bowel Disease Treatment

“…Micromotors are artificial microdevices that can realize autonomous movement through energy conversion. − To meet the requirement of different applications, micromotors in copious morphologies have been devised with diverse propulsion mechanisms. − Among them, NIR-II light (1000–1700 nm), which can provide deeper penetration, lower tissue autofluorescence, and photoscattering, has come to the forefront as an emerging external stimulus to drive micromotors to move autonomously in vivo. − In contrast, pollen grains, which are nature-derived microscale particles, are identified as an ideal carrier for drug delivery because their special architecture with an inner hollow cavity and porous surface endows them with high cargo-loading capacity. − Besides, their spiny structure on the surface endows them with a large area for contacting, thus enhancing their property for adherence. − Therefore, it is conceived that an outstanding kind of active adhesive delivery system can be developed for efficient gastrointestinal drug delivery by combining micromotors, NIR-II light, and pollen.…”