State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan 430070, China.
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan 430070, China; Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, Wuhan University of Technology, Wuhan 430070, China.
J Colloid Interface Sci. 2025 Feb;679(Pt A):747-759. doi: 10.1016/j.jcis.2024.10.011. Epub 2024 Oct 4.
Hyperglycemia-promoted bacterial infection will seriously exacerbate diabetic wounds, and its current clinical treatments are suffering from the adverse effects associated with off-target, bacterial resistance, and glycemic fluctuation. Herein, we present a kind of glucose-fueled cationic nanomotors capable of remarkably enhancing antibacterial efficacy, and thus expediting diabetic wound healing. The nanomotors have positively charged surfaces, and consist of mesoporous bowl-shaped polydopamine nanoparticles grafted with quaternized polymer brushes and coupled with glucose oxidase (GOx) and catalase (CAT). Stemming from the GOx-CAT cascade reaction in diabetic wound microenvironment, they can perform robust chemotactic motion towards both high glucose regions, where bacteria proliferation predominantly occurs, and elevated HO levels, which bacterial metabolism produced. This enables the nanomotors to facilitate targeted migration towards bacteria-rich regions and simultaneous downregulation of glycemic levels, as well as to significantly enhance the electrostatic interaction between antibacterial components and bacteria. Consequently, the nanomotors exhibit amplified contact-killing effects of their attached cationic molecules, leading to an almost 10-fold enhancement in antibacterial efficacy compared to previous counterparts. The in vivo experiments approved that the nanomotors demonstrated the accelerated healing of infected diabetic wounds by S. aureus and biosafety. The results herein provide an insight into the clinical treatment of infected diabetic wounds.
高血糖促进的细菌感染会严重恶化糖尿病伤口，目前的临床治疗方法受到与非靶点相关的副作用、细菌耐药性和血糖波动的影响。在此，我们提出了一种葡萄糖驱动的阳离子纳米马达，能够显著增强抗菌效果，从而加速糖尿病伤口愈合。纳米马达具有带正电荷的表面，由介孔碗状聚多巴胺纳米粒子与季铵化聚合物刷接枝，并与葡萄糖氧化酶 (GOx) 和过氧化氢酶 (CAT) 偶联而成。源自糖尿病伤口微环境中的 GOx-CAT 级联反应，它们能够针对高葡萄糖区域（细菌增殖主要发生的区域）和升高的 HO 水平（细菌代谢产生的水平）进行强大的趋化运动。这使得纳米马达能够促进向富含细菌的区域的靶向迁移，并同时降低血糖水平，同时增强抗菌成分与细菌之间的静电相互作用。因此，纳米马达表现出附着的阳离子分子的增强接触杀伤效应，与以前的对应物相比，抗菌效果提高了近 10 倍。体内实验证实，纳米马达通过金黄色葡萄球菌加速了感染性糖尿病伤口的愈合，并具有生物安全性。本文的结果为感染性糖尿病伤口的临床治疗提供了新的思路。
