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

Journal of Nanobiotechnology

Yanmei Yang¹  Mingwen Zhao²  Weifeng Li²  Weijie Wang²  Bingqing Jia²  Yuanyuan Qu²  Xiangdong Liu²  Xuancheng Du²  Yong-Qiang Li³  Chengmei Zhang⁴ 

[1] College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, 250014, Jinan, China;Institute of Advanced Interdisciplinary Science, School of Physics, Shandong University, 250100, Jinan, China;Institute of Advanced Interdisciplinary Science, School of Physics, Shandong University, 250100, Jinan, China;Suzhou Research Institute, Shandong University, 215123, Suzhou, China;Laboratory Animal Center of Shandong University, 250012, Jinan, China;

关键词: Biofilm eradication;    Cascade catalysis;    Diabetic ulcer;    Nanozyme;    Pathological microenvironment modulation;   

DOI  :  10.1186/s12951-021-01215-6

来源: Springer

【 摘 要 】

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 (Fe3O4-GOx). The Fe3O4-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 phases significantly speed up the normal orchestrated wound-healing cascades. Remarkably, this Fe3O4-GOx-instructed spatial–temporal remodeling of DU microenvironment enables complete re-epithelialization of biofilm-infected wound in diabetic mice within 15 days while minimizing toxicity to normal tissues, exerting great transformation potential in clinical DU management. The proposed PNCC concept offers a new perspective for complex pathological microenvironment remodeling, and may provide a powerful modality for the treatment of microenvironment-associated diseases.Graphical Abstract

【 授权许可】

CC BY