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.

Coordination‐Driven One‐Step Rapid Self‐Assembly Synthesis of Dual‐Functional Ag@Pt Nanozyme

“…[26] Chen and his colleagues developed aptamer-functionalized nanozymes which specifically target pathogenic bacteria by surface-decorated aptamer nanozyme with POD-like activity in the microenvironment of glucose catalyzed by glucose oxidase. [27] Based on the above studies, POD-like nanozyme usually Catalytic production of ROS to achieve the inhibition of pathogenic bacteria, and can be applied to eliminate microorganisms, tumors, and cancer therapy. [28,29] Therefore, the dual-functional Ag@Pt nanozyme was first synthesized by DNA and metal ions coordination-driven onestep rapid self-assembly methods.…”

Glucose Oxidase Energized Osmium with Dual‐Active Centers and Triple Enzyme Activities for Infected Diabetic Wound Management

“…Moreover, these systems replenish the concentration of H 2 O 2 at the site of infection and avoid potential damage to normal tissues caused by externally added H 2 O 2 . [32] Generated gluconic acid during the GOx-catalyzed reaction could decrease the pH and activate the peroxidase-like activity of nanozymes. For instance, Du et al created an iron oxide (Fe 3 O 4 ) nanozyme with peroxidase-like and GOx activities by electrostatic coating and covalently modifying GOx, which could effectively eliminate biofilm infection in diabetic wounds and accelerate healing.…”

“…Moreover, these systems replenish the concentration of H 2 O 2 at the site of infection and avoid potential damage to normal tissues caused by externally added H 2 O 2 . [ 32 ] Generated gluconic acid during the GOx‐catalyzed reaction could decrease the pH and activate the peroxidase‐like activity of nanozymes. For instance, Du et al.…”

Recent progress in nanozymes for the treatment of diabetic wounds

“…Thus, the infectious pathogens in the wound are eliminated, and wound healing is promoted. 25 (2) Reducing blood glucose levels in the diabetic wound. Nanozymes with glucose oxidase-like (GOx) activity can convert glucose in the wound into gluconic acid and H 2 O 2 , which not only can reduce the blood sugar, but also can produce H 2 O 2 as the substrate of the nanozyme, further generating more ˙OH to strengthen the bacterial removal effect and relieving the hyperglycemic environment.…”