A Copper Single‐Atom Cascade Bionanocatalyst for Treating Multidrug‐Resistant Bacterial Diabetic Ulcer

Abstract

Diabetic ulcers induced by multidrug‐resistant (MDR) bacteria have severely endangered diabetic populations. These ulcers are very challenging to treat because the local high glucose concentration can both promote bacterial growth and limit the immune system's bactericidal action. Herein, a glucose oxidase‐peroxidase (GOx‐POD) dual‐enzyme mimetic (DEM) bionanocatalyst, Au@CuBCats is synthesized to simultaneously control glucose concentration and bacteria in diabetic ulcers. Specifically, the AuNPs can serve as GOx mimics and catalyze the oxidation of glucose for the formation of H2O2; the H2O2 can then be further catalytically converted into OH via the POD‐mimetic copper single atoms. Notably, the unique copper single atoms coordinated by one oxygen and two nitrogen atoms (CuN2O1) exhibit better POD catalytic performance than natural peroxidase. Further DFT calculations are conducted to study the catalytic mechanism and reveal the advantage of this CuN2O1 structure as compared to other copper single‐atom sites. Both in vitro and in vivo experiments confirm the outstanding antibacterial therapeutic efficacy of the DEM bionanocatalyst. This new bionanocatalyst will provide essential insights for the next generation of antibiotic‐free strategies for combating MDR bacterial diabetic ulcers, and also offer inspiration for designing bionanocatalytic cascading medicines.

Exploring the Inner- and Outer-Sphere Mechanistic Pathways of ORR on M–N–Cs with Pyrrolic MN4 Motifs

“…In particular, the exergonic formation of the *­(OH) 2 intermediate implies a significant driving force toward the dissociation of H 2 O 2 at these sites. While such an interaction is consistent with the relatively high H 2 O 2 RR currents measured on Mn–N–Cs and Fe–N–Cs and the generally high 4e-ORR selectivity of the latter, it can have detrimental effects on the stability of these active sites, one of the key limitations reported in Fe–N–C catalysts. , In particular, if either of the OH fails to bind to the metal upon dissociation of H 2 O 2 , OH radicals could be produced in a Fenton-like reaction, inducing oxidative stress on the carbon matrix. ,− Such a process is especially relevant in acidic media where the H 2 O 2 remains in its protonated form. , Therefore, although the complementary outer-sphere mechanism is theoretically favorable for producing higher currents, it could in fact be detrimental to the corrosion resistance of metals such as Cr and Fe in the pyrrolic MN 4 site due to their strong interactions with H 2 O 2 . In order to increase the long-term stability of such materials, modifications should be targeted at either decreasing the relative contribution of the outer-sphere mechanism (but potentially leading to smaller currents) or minimizing interactions of FeN 4 sites with H 2 O 2 , for example, by providing alternative active sites for H 2 O 2 RR that do not produce OH radicals.…”

“…While such an interaction is consistent with the relatively high H 2 O 2 RR currents measured on Mn−N−Cs and Fe−N−Cs 62 and the generally high 4e-ORR selectivity of the latter, it can have detrimental effects on the stability of these active sites, one of the key limitations reported in Fe−N−C catalysts. 7,63 In particular, if either of the OH fails to bind to the metal upon dissociation of H 2 O 2 , OH radicals could be produced in a Fenton-like reaction, 64 inducing oxidative stress on the carbon matrix. 63,65−67 Such a process is especially relevant in acidic media where the H 2 O 2 remains in its protonated form.…”

Reactive oxygen nanobiocatalysts: activity-mechanism disclosures, catalytic center evolutions, and changing states

“…In addition, novel target-oriented characterisation techniques, especially in situ methods, such as in situ XAS, in situ XRD, and also in situ Raman, have emerged as frontier techniques to perform real-time monitors for a better understanding of the catalytic mechanisms, thus facilitating the DFT calculation, and guiding the future design of catalysts also deserves more attention to clearly detect the complex catalytic conversion chemistry and to reveal the catalytic mechanisms of RONBCs. 303–305…”

Pore-Forming Toxin-Driven Recovery of Peroxidase-Mimicking Activity in Biomass Channels for Label-Free Electrochemical Bacteria Sensing

“…This can be attributed to the large amount of sugar in juice, which is a nutrient ideal for bacterial proliferation. 54 Consequently, elevated bacterial activity leads to the production of more α-toxin. The above results demonstrate that the proposed electrochemical channel sensing strategy is reliable in real applications and has good potential for the practical detection of food toxins.…”