Wang Yingshuai, Shi Lihua, Lu Junna, Wang Fengyuan, Zhou Zihan, Wang Yuexuan, Du Xiangyu, Qin Di, Chen Fangman, Shao Dan, Gao Yuanyuan, Gao Cheng, Sun Tongyi
Shandong Key Laboratory of Proteins and Peptides Pharmaceutical Engineering, Shandong Universities Key Laboratory of Biological Medicine, School of Life Science and Technology, Shandong Second Medical University, 7166 # Baotong West Street, Weifang, Shandong, 261053, People's Republic of China.
School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong, 510006, People's Republic of China.
J Nanobiotechnology. 2025 Jan 30;23(1):62. doi: 10.1186/s12951-025-03115-5.
Diabetic foot ulcers (DFU) are severe complications of diabetes, posing significant health and societal challenges. Accumulation of reactive oxygen species (ROS) and elevated glucose levels are primary factors affecting diabetic wound healing. Achieving effective treatment by reducing ROS alone is challenging, as high glucose levels continuously drive ROS production. The excellent glucose-consuming capacity of lactobacilli and the antioxidant function of hydrogen undoubtedly provide good therapeutic ideas. Herein, we combined probiotic Lactobacillus reuteri with acid-responsive hydrogen-producing nanoparticles to construct probiotic active gel LR&AB@CAH to enable a cascade of glucose consumption and hydrogen production. Lactobacillus reuteri consumed overproduced glucose and thereby released lactic acid to activate nanoparticle for hydrogen production, which could neutralize excess ROS and promote wound healing.
In vitro experiments demonstrate that LR&AB@CAH has good biocompatibility, antioxidant capacity. LR&AB@CAH reduces excess ROS, decreases oxidative substances, and boosts antioxidant enzyme activity. In a diabetic wound mouse model, it functions as a glucose scavenger and antioxidant, reducing ROS and supporting wound healing.
LR&AB@CAH offers a novel strategy for the comprehensive treatment of DFU. This study provides an artificial-natural composite hydrogel for cascade therapy on diabetic wound healing, and suggests a complete management approach for diabetic oxidative stress.
糖尿病足溃疡（DFU）是糖尿病的严重并发症，给健康和社会带来重大挑战。活性氧（ROS）的积累和血糖水平升高是影响糖尿病伤口愈合的主要因素。仅通过减少ROS来实现有效治疗具有挑战性，因为高血糖水平会持续驱动ROS的产生。乳酸杆菌出色的葡萄糖消耗能力和氢气的抗氧化功能无疑提供了良好的治疗思路。在此，我们将益生菌罗伊氏乳杆菌与酸响应性产氢纳米颗粒相结合，构建了益生菌活性凝胶LR&AB@CAH，以实现葡萄糖消耗和氢气产生的级联反应。罗伊氏乳杆菌消耗过量的葡萄糖，从而释放乳酸以激活纳米颗粒产氢，这可以中和过量的ROS并促进伤口愈合。
体外实验表明LR&AB@CAH具有良好的生物相容性和抗氧化能力。LR&AB@CAH可减少过量的ROS，降低氧化物质，并提高抗氧化酶活性。在糖尿病伤口小鼠模型中，它作为葡萄糖清除剂和抗氧化剂发挥作用，减少ROS并支持伤口愈合。
LR&AB@CAH为DFU的综合治疗提供了一种新策略。本研究为糖尿病伤口愈合的级联治疗提供了一种人工-天然复合水凝胶，并提出了一种针对糖尿病氧化应激的完整管理方法。
