pH-switchable nanozyme cascade catalysis: a strategy for spatial–temporal modulation of pathological wound microenvironment to rescue stalled healing in diabetic ulcer

作者：Xuancheng Du, Bingqing Jia, Weijie Wang, Chengmei Zhang, Xiangdong Liu, Yuanyuan Qu, Mingwen Zhao, Weifeng Li, Yanmei Yang, Yongqiang Li · 发表于：Journal of Nanobiotechnology · 年份：2022 · DOI：10.1186/s12951-021-01215-6 · 被引用次数：133 · 研究领域：Advanced Nanomaterials in Catalysis、Wound Healing and Treatments、Graphene and Nanomaterials Applications

Abstract The management of diabetic ulcer (DU) to rescue stalled wound healing remains a paramount clinical challenge due to the spatially and temporally coupled pathological wound microenvironment that features hyperglycemia, biofilm infection, hypoxia and excessive oxidative stress. Here we present a pH-switchable nanozyme cascade catalysis (PNCC) strategy for spatial–temporal modulation of pathological wound microenvironment to rescue stalled healing in DU. The PNCC is demonstrated by employing the nanozyme of clinically approved iron oxide nanoparticles coated with a shell of glucose oxidase (Fe 3 O 4 -GOx). The Fe 3 O 4 -GOx possesses intrinsic glucose oxidase (GOx), catalase (CAT) and peroxidase (POD)-like activities, and can catalyze pH-switchable glucose-initiated GOx/POD and GOx/CAT cascade reaction in acidic and neutral environment, respectively. Specifically, the GOx/POD cascade reaction generating consecutive fluxes of toxic hydroxyl radical spatially targets the acidic biofilm (pH ~ 5.5), and eradicates biofilm to shorten the inflammatory phase and initiate normal wound healing processes. Furthermore, the GOx/CAT cascade reaction producing consecutive fluxes of oxygen spatially targets the neutral wound tissue, and accelerates the proliferation and remodeling phases of wound healing by addressing the issues of hyperglycemia, hypoxia, and excessive oxidative stress. The shortened inflammatory phase temporally coupled with accelerated proliferation and remodeling p...