团队博士生林金卫、许蕾蕾研究员等联合我校生物中心戴红莲教授课题组撰写的论文“Hyperglycemia Targeting Nanomotors for Accelerated Healing of Diabetic Wounds by Efficient Microenvironment Remodeling”被期刊Advanced Functional Materials（2024年IF：18.1，中科院一区TOP期刊）接收（DOI: 10.1002/adfm.202417146）
多功能纳米制剂现阶段使用的纳米粒子在伤口中主要依赖于被动布朗扩散以及随机增强扩散，基本上不具备深度扩散和靶向能力，是限制多功能纳米制剂治疗效果的主要因素之一。在这里，我们考虑到糖尿病伤口周围存在葡萄糖浓度分布不均一这种异质性，设计了一种由内源性葡萄糖激活的级联反应驱动的Janus纳米马达。这种马达在生理葡萄糖浓度下能展现出增强扩散的特性，并在具有相应生理葡萄糖浓度梯度的环境下表现出向高葡萄糖浓度定向迁移的趋化行为。当用其处理糖尿病伤口时，它们能够有效地靶向糖尿病伤口的高糖界面，并表现出增强富集与渗透行为，显著加速伤口愈合。与以前的同类产品相比，它们结合葡萄糖氧化酶与过氧化氢酶的级联反应，在60秒内的有效覆盖率能提高4倍，在高血糖界面的积累成倍增加，促进深度渗透。因此，血糖水平和pH下调明显增强，供氧改善。与被动扩散和随机增强扩散体系相比，基于该高血糖靶向纳米马达制成的喷雾剂由于能同步实现葡萄糖的消耗和ROS有效清除的、以及环境pH的降低，因而能抑制伤口的炎症反应，增强巨噬细胞的M2分化，提高血管内皮生长因子水平，可使糖尿病小鼠的伤口愈合速度加快约30%和23%。本研究提出了一种利用伤口微环境的异质性可构建靶向递送体系，提升靶向治疗效果的通用有效方法，这可以扩展到其他治疗系统。
原文摘要如下：Multifunctional nanoagents are robust to remodel environments for managing chronic diabetic wounds. However, their delivery primarily relies on Brownian motion and randomly enhanced diffusion. Here, taking advantages of wound heterogeneity, such as the uneven distribution of glucose, we propose hyperglycemia targeting nanomotors. They are capable of efficiently targeting to hyperglycemic interfaces in diabetic wounds for significantly accelerating their healing by employing endogenous glucose-activated cascade reactions and responding to local glucose gradients. Compared to previous counterparts, they show a four-fold enhancement in effective coverage within 60 seconds and a multiplied accumulation at hyperglycemic interfaces, facilitating deep penetration. Correspondingly, the downregulation of glucose levels is apparently enhanced, while pH-lowering and oxygen-supplying are both improved. In comparison to the counterparts delivered by passive diffusion and random enhanced diffusion, the hyperglycemia targeting nanomotor-based spray accelerates the wound healing upon diabetic mice by approximately 30 % and 23%, resulting from the restricted inflammatory response, effective reactive oxygen species scavenging and elevated vascular endothelial growth factor levels. This study presents a general efficient approach to facilitate targeted delivery of nanoagents for the effective management of diabetic wounds by utilizing wound heterogeneity, which can be extended to other therapeutic systems.
