Bimetallic CuCo₂S₄ Nanozymes with Enhanced Peroxidase Activity at Neutral pH for Combating Burn Infections

Abstract

Peroxidase‐mimicking nanozymes that can generate toxic hydroxyl radicals (.OH) hold great promise as antibacterial alternatives. However, most of them display optimal performance under strongly acidic conditions (pH 3–4), and are thus not feasible for many medical uses, including burn infections with a wound pH close to neutral. Herein, we report a copper‐based nanozyme (CuCo2S4) that exhibits intrinsic peroxidase‐like activity and can convert H2O2 into .OH at neutral pH. In particular, bimetallic CuCo2S4 nanoparticles (NPs) exhibited enhanced peroxidase‐like activity and antibacterial capacity, superior to that of the corresponding monometallic CuS and CoS NPs. The CuCo2S4 nanozymes possessed excellent ability to kill various bacteria, including methicillin‐resistant Staphylococcus aureus (MRSA). Furthermore, this CuCo2S4 nanozymes could effectively disrupt MRSA biofilms in vitro and accelerate MRSA‐infected burn healing in vivo. This work provides a new peroxidase mimic to combat bacteria in neutral pH milieu and this CuCo2S4 nanozyme could be a promising antibacterial agent for the treatment of burn infections.

Reducing Biofilm Infections in Burn Patients’ Wounds and Biofilms on Surfaces in Hospitals, Medical Facilities and Medical Equipment to Improve Burn Care: A Systematic Review

“…A comparison of eleven antimicrobial burn dressings found that 72 h after infection with A. baumanii , two silver formulations reduced A. baumanii numbers in biofilms (commercial silver formulations Acticoat by 96%, Mepilex Ag by 95.9%) and acetic acid by 90–93%. P. aeruginosa numbers were reduced by Acticoat by 100%, Mepilex Ag by 100% and acetic acid by 86–93% [ 15 ].…”

“…After six days the group treated with H 2 O 2 at 2 nM and CuCo 2 S 4 at 100 μg/mL showed enhanced healing and 83.7% wound closure, with CuCo 2 S 4 71%, with H 2 O 2 63.3%, and the control 59%. At two weeks, the H 2 O 2 , and CuCo 2 S 4 - treated wounds were completely closed and healed [ 15 ].…”

“…Interventions meriting further testing on the basis of one or more outcome measures have been starred *** in Table 1 . These include Gholamrezazadeh’s study of nano-silver [ 6 ], Pourhajibagher’s study of AgSD-NLs@Cur [ 14 ], Halstead’s studies of silver (Acticoat, Mepilex) and acetic acid [ 13 , 17 ], Karaky’s study of graphene–metal combinations [ 8 ], Li’s study of CuCo 2 S 4 nanoparticles [ 15 ], Song’s study of Chlorhexidene acetate nanoemulsion (CNE) [ 18 ], Chhibber’s study of a novel hydrogel (moxifloxacin, carbomer, Chitosan, and Boswellia) [ 20 ], Pourhajibagher’s study of nano-emodin to release reactive oxygen species (ROS) [ 21 ], Lu’s study of blue light + carvacrol [ 3 ], Wang’s study of antimicrobial blue light [ 4 ], Banar’s study of mannosidase + trypsin [ 23 ], Ghosh’s study of NCK-10, a naphthalene core compound with a decyl chain appendage [ 1 ], Han’s study of AMP-jsa9 [ 25 ], Ghosh’s study of NCK-10 [ 24 ], Konai’s study of D-LANA [ 5 ], Memariani’s study of the antimicrobial peptide PV3, which includes two snake venoms [ 26 ], Pan’s study of the polypeptides P03 and PL2 [ 27 ], and the studies of phage therapy by Ho [ 34 ] and O’Flaherty [ 36 ]. Replications in large RCTs using animal models then in c-RCTs of patients, surfaces in hospital, and medical facility and medical equipment and using uniform experimental methods would best be accomplished by a large consortium of burn researchers.…”

Engineered Nanoenzymes with Multifunctional Properties for Next‐Generation Biological and Environmental Applications

“…[ 11,28 ] When using the oxidizing enzyme and nanoenzyme with different optimal activities, there was a hassle of changing the buffer to change pH after the oxidizing step, which made it impossible to develop into a practical application. [ 29 ] To overcome this shortcoming, only a few kinds of metal‐based nanoenzymes have been reported to have peroxidase‐like activity at near‐neutral pH including bimetallic CuCo 2 S 4 , [ 30 ] cobalt‐based polyoxometalate (CoPW 11 O 39 ), [ 31 ] and 2D MOF (2D Cu TCPP(Fe). [ 32 ] Moreover, a few studies have developed effective methods to adjust the working pH range of metal nanoenzymes, based primarily on surface charge engineering.…”

A Review on Metal- and Metal Oxide-Based Nanozymes: Properties, Mechanisms, and Applications

“…After the pioneering work of Gao et al [ 6 ] reporting ferromagnetic (Fe 3 O 4 ) nanoparticles (NPs) with enzyme-mimicking property in 2007, a bunch of nanozymes have been demonstrated as natural catalysts mimics. For instance, Au@Co–Fe hybrid NPs [ 7 ], CuCo 2 S 4 NPs [ 8 ], MnO 2 nanowires (NWs) [ 9 ], Pt nanoclusters (NCs) [ 10 ], Au@Pt nanorods (NRs) [ 11 ], and carboxyl-modified graphene oxide (GO–COOH) [ 12 ] have been reported as peroxidase (POD) mimics. Nanozymes with multi-enzyme-type activities (e.g., Co(OH) 2 /FeOOH/WO 3 ternary nanoflowers [ 13 ], AuNPs [ 14 , 15 ], Co 3 O 4 NPs [ 16 ], AgPt NPs [ 17 ], N-doped sponge-like carbon spheres [ 18 ], Mn 3 O 4 NPs [ 19 ]) have been exploited in diverse investigation.…”