Recent Advances in Nanozymes Toward Diabetic Foot Ulcers

Shiyang Zhou,1,* Jiayin Deng,1,* Tianji Feng,2 Peifang Dong1 1Nursing Department of Eye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, People’s Republic of China; 2MOE Key Laboratory of Macromolecule Synthesis and Functionalization of the Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310058, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tianji Feng, MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310058, People’s Republic of China, Email [email protected] Peifang Dong, Nursing Department of Eye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, People’s Republic of China, Email [email protected]: Diabetic foot ulcers (DFUs) are one of the most serious and intractable complications of diabetes, caused by oxidative stress due to hyperglycemia, chronic inflammation, and repeated infections. Conventional treatments such as insulin therapy do not improve the pathological wound microenvironment, resulting in slow healing and a high rate of recurrence. Nanozymes, with superior catalytic stability, tuneable enzyme-like activities, and multifunctional synergy, have emerged as a promising therapeutic strategy. Nanozymes that imitate natural enzymes such as glucose oxidase, peroxidase, catalase, and superoxide dismutase can actively remodel the DFUs microenvironment via glucose depletion, dynamic regulation of reactive oxygen species, disruption of biofilm, suppression of inflammation, and oxygen generation. These integrated functions can help wounds heal faster, and they can promote angiogenesis and tissue regeneration. This review discusses recent advances in catalytic mechanisms and therapeutic applications of nanozymes for DFUs management, with special attention paid to the microenvironment-responsive systems, hydrogel-based composites, and synergistic photothermal or drug delivery platforms. Lastly, the current issues of biosafety, catalytic efficiency, and target accuracy are mentioned, followed by future directions for clinical application.Keywords: nanozymes, diabetic foot ulcers, wound microenvironment, enzyme-like activity, multifunctional therapy