A Glucose‐Powered Activatable Nanozyme Breaking pH and H₂O₂ Limitations for Treating Diabetic Infections

Abstract

The peroxidase‐like activity of nanozymes is promising for chemodynamic therapy by catalyzing H2O2 into .OH. However, for most nanozymes, this activity is optimal just in acidic solutions, while the pH of most physiological systems is beyond 7.0 (even >8.0 in chronic wounds) with inadequate H2O2. We herein communicate an activatable nanozyme with targeting capability to simultaneously break the local pH and H2O2 limitations under physiological conditions. As a proof of concept, aptamer‐functionalized nanozymes, glucose oxidase, and hyaluronic acid constitute an activatable nanocapsule “APGH”, which can be activated by bacteria‐secreted hyaluronidase in infected wounds. Nanozymes bind onto bacteria through aptamer recognition, and glucose oxidation tunes the local pH down and supplements H2O2 for the in‐situ generation of .OH on bacteria surfaces. The activity switching and enhanced antibacterial effect of the nanocapsule were verified in vitro and in diabetic wounds. This strategy for directly regulating local microenvironment is generally accessible for nanozymes, and significant for facilitating biological applications of nanozymes.

Efficient nanozyme engineering for antibacterial therapy

“…Besides, the Arrhenius equation demonstrates the chemical reaction rate significantly dependent on temperature [88]. Thus, starting from these basic principles, proper external stimuli such as ATP [40,89], glucose [90], visible light irradiation [39], and NIR light irradiation [91], AMF [92] can enhance the catalytic reaction process of nanozymes through H + , H 2 O 2 , H 2 O 2 affinity, thermal, and active ion concentration modulations, thereby resulting in significantly enhanced bactericidal efficiency of nanozymes under low H 2 O 2 concentration and even neutral pH.…”

“…With the aid of ATP, owing to its ability of participation in single electron transfer reaction through complexation with Fe 3 O 4 NPs [96,97], the •OH generation catalyzed by Fe 3 O 4 NPs could be significantly accelerated, resulting in enhanced bactericidal efficiency in presence of H 2 O 2 at neutral pH [38] (figure 3(A)). To break the limitations of local pH and H 2 O 2 under physiological conditions, instead of ATP, Chen et al have constructed a versatile glucose-stimulated nanozymes composed of aptamer-functionalized platinum nanozymes (Apt-PtNZ), glucose oxidase (GOX) and hyaluronic acid (HA) (denoted as APGH) for treating diabetic infections (pH = 7.0-8.0) [90]. With aptamer recognition, APGH could first adhere to bacterial surface, then glucose oxidase would catalyze the glucose oxidation to generate H 2 O 2 and lower the local pH, and finally the POD-mimicking Pt NPs in-situ converted the H 2 O 2 into •OH on bacteria surfaces, subsequently enhancing the antibacterial effect in vitro and in diabetic wounds [90] (figure 3(B)).…”

“…NO, Ag + , Zn 2+ , carvacrol) release for enhancing chronic wound healing [112][113][114][115]. Cascaded nanozymes that can trigger POD-, catalase-, and glucose oxidase-like catalysis have shown great potential for diabetic wound recovery due to the coupling of glucose consumption, antibacterial and anti-inflammatory activity [90,[116][117][118]. Moreover, the MOF 2.5Au-Ce nanozymes with dual POD and deoxyribonuclease (DNase) and POD mimetic activities displayed significantly enhanced biofilm disruption efficiency [59].…”

Acidic microenvironment triggered in situ assembly of activatable three-arm aptamer nanoclaw for contrast-enhanced imaging and tumor growth inhibition in vivo

“…To meet these requirements, multivalent aptamer probes, by integrating multiple aptamer units into one nanomaterial or DNA nanostructure, have been employed to enhance the binding affinity via the multivalent effect. It has been shown the multivalent aptamer probes strategy increased local ligand density or synergistic interaction 13 - 15 . In particular, benefiting from the great progress of DNA nanotechnology, series of DNA nanostructures including DNA tetrahedron 10 , 16 , 17 , DNA nanowire 18 , DNA nanohydrogel 19 , 20 , RCA-based DNA nanostructure 21 , 22 , etc., have been exploited and used as scaffolds to incorporate multivalent aptamers.…”

Colorimetric and Fluorescence Dual-Mode Biosensors Based on Peroxidase-Like Activity of the Co3O4 Nanosheets

“…Many nanomaterials, such as cobaltosic oxide nanoparticles ( Wang P. et al, 2019 ), manganese dioxide ( Zou et al, 2021 ), graphene oxide hybrid ( Wang Q. et al, 2021 ; Zhang et al, 2021e ), nanoceria ( Zhang J. et al, 2021 ), carbon dots ( Li et al, 2022 ), VS 2 ( Huang et al, 2018 ), PtS 2 ( Zhang W. et al, 2021 ), MoS 2 ( Zhang X. et al, 2021 ; Tan et al, 2021 ), and WS 2 ( Nandu et al, 2021 ), had been shown to possess a similar peroxidase-like activity. These nanozymes had been used in various fields including biosensing ( Wang L. et al, 2021 ; Liu et al, 2021 ), bioimaging ( Gao et al, 2017 ; Liu et al, 2019 ), therapeutics ( Chen et al, 2021 ; Zhang et al, 2021d ; Zhang et al, 2021e ; Hai et al, 2021 ), and biofuel cells ( Le and Il, 2021 ) as substitutes for natural enzymes. Among these nanozymes, Co 3 O 4 nanomaterials exhibit multienzyme activities at different pH conditions ( Wang P. et al, 2019 ) which had been used to construct enzyme-free glucose sensors and other biosensing applications.…”