Near-Infrared-Controlled Nanoplatform Exploiting Photothermal Promotion of Peroxidase-like and OXD-like Activities for Potent Antibacterial and Anti-biofilm Therapies

Abstract

Nanozymes that mimic peroxidase (POD) activity can convert H2O2 into bactericidal free radicals, which is referred to as chemodynamic therapy (CDT). High glutathione (GSH) levels in the infectious tissue severely limit the performance of CDT. Herein, we report a near-infrared-controlled antibacterial nanoplatform that is based on encapsulating tungsten sulfide quantum dots (WS2QDs) and the antibiotic vancomycin in a thermal-sensitive liposome. The system exploits the photothermal sensitivity of the WS2QDs to achieve selective liposome rupture for the targeted drug delivery. We determined that WS2QDs show a strong POD-like activity under physiological conditions and the oxidase-like activity, which can oxidate GSH to further improve the CDT efficacy. Moreover, we found that increased temperature promotes multiple enzyme-mimicking activities of WS2QDs. This platform exerts antibacterial effects against Gram-positive Mu50 (a vancomycin-intermediate Staphylococcus aureus reference strain) and Gram-negative Escherichia coli and disrupts biofilms for improved penetration of therapeutic agents inside biofilms. In vivo studies with mice bearing Mu50-caused skin abscess revealed that this platform confers potent antibacterial activity without obvious toxicity. Accordingly, our work illustrates that the photothermal and nanozyme properties of WS2QDs can be deployed alongside a conventional therapeutic to achieve synergistic chemodynamic/photothermal/pharmaco therapy for powerful antibacterial effects.

Copper single-atom catalysts with photothermal performance and enhanced nanozyme activity for bacteria‐infected wound therapy

“…A large number of •OH produced by peroxidase-like nanozymes can be depleted by GSH, and the concentration increases significantly at the infection sites due to the abnormal encapsulation of extracellular polymeric substances [ 19 ]. Copper-based catalysts usually have good GSH depletion capabilities due to their multivalent properties [ 32 ].…”

“…Unfortunately, the low catalytic activity of nanozymes greatly limits their antibacterial effects [ 18 ]. In addition, it is also worth noting that the microenvironments of the infection sites usually have abnormally high expression of glutathione (GSH) levels, which are caused by anaerobic glycolysis, greatly reducing the catalytic therapeutic effects of nanozymes [ [19] , [20] , [21] ]. Thus, there is still a great need for antibacterial nanozymes with enhanced catalytic activity and GSH-depleting function.…”

Peroxidase Mimetic Nanozymes in Cancer Phototherapy: Progress and Perspectives

“…Besides the therapeutic platform, incorporating Au NPs into mesoporous carbon can facilitate the action of POD mimitic activity and generate ROS for intracellular oxidative damage of cancer cells. As shown in Figure 5 In addition to the previously mentioned advantages of nanozymes in cancer therapeutics, several further POD mimetic nanozyme platforms such as Au@Co-Fe NPs [72], CuO Nanorods [73], Fe3O4@MoS2-Ag nanozyme [74], Pd nanocrystals [75], and Pt hollow nanodendrites [76], N-doped spongelike carbon spheres (N-SCSs) [77], PEGylated palladium nanozyme (Pd-PEG) [78], tungsten sulfide quantum dots (WS2 QDs) [79], nickel disulfide (ND) nanozyme [80], iridium (Ir) nanoplates [81] and MoS2 [82] have been successfully utilized in antibacterial applications with significant outcomes. Table 1 summarizes POD-based nanozyme applications in cancer phototherapeutics.…”

Accelerated antibacterial red-carbon dots with photodynamic therapy against multidrug-resistant Acinetobacter baumannii

“…We wished to ascertain if R-CDs or ROS could destroy the integrity of the cell walls and cell membranes of bacteria. A live/ dead bacterial viability kit was used to stain treated bacteria followed by CLSM [15,53,54]. Live bacterial cells showed a green fluorescence signal.…”

“…More than 60% of human infectious diseases are attributed to bacterial biofilms, which contribute to their tolerance of antibiotic treatment [3,54]. Encouraged by the attractive antibacterial activities of R-CDs, we extended antibacterial tests to eliminate MRAB biofilms in vitro.…”