Abstract：
Considerable progress has been made in the development of drug delivery systems for diabetic wounds. However, underlying drawbacks, such as low delivery efficiency and poor tissue permeability, have rarely been addressed. In this study, a multifunctional biohybrid nanorobot platform comprising an artificial unit and several biological components is constructed. The artificial unit is a magnetically driven nanorobot surface modified with antibacterial 2-hydroxypropyltrimethyl ammonium chloride chitosan, which enables the entire platform to move and has excellent tissue penetration capacity. The biological components are two-step engineered extracellular vesicles that are first loaded with mangiferin, a natural polyphenolic compound with antioxidant properties, and then glycoengineered on the surface to enhance cellular uptake efficiency. As expected, the platform is more easily absorbed by endothelial cells and fibroblasts and exhibits outstanding dermal penetration performance and antioxidant properties. Encouraging results are also observed in infected diabetic wound models, showing improved wound re-epithelialization, collagen deposition, angiogenesis, and accelerated wound healing. Collectively, a biohybrid nanorobot platform that possesses the functionalities of both artificial units and biological components serves as an efficient delivery system to promote diabetic wound repair through dual-enhanced cell and tissue penetration and multistep interventions.
摘要：
在开发用于糖尿病伤口的药物递送系统方面已经取得了相当大的进展。然而,潜在的缺点，如输送效率低和组织渗透性差，很少被解决。在这项研究中,构建了包括人工单元和若干生物组件的多功能生物混合纳米机器人平台。人工单元是用抗菌2-羟丙基三甲基氯化铵壳聚糖表面修饰的磁驱动纳米机器人，这使得整个平台移动，并具有优良的组织穿透能力。生物成分是两步工程的细胞外囊泡，首先装载芒果苷，一种具有抗氧化性能的天然多酚化合物，然后在表面进行糖工程以增强细胞摄取效率。不出所料,该平台更容易被内皮细胞和成纤维细胞吸收，并表现出突出的皮肤渗透性能和抗氧化性能。在感染的糖尿病伤口模型中也观察到令人鼓舞的结果，显示伤口上皮再生改善，胶原蛋白沉积，血管生成,加速伤口愈合。总的来说，具有人工单元和生物组分功能的生物混合纳米机器人平台作为有效的递送系统,通过双重增强的细胞和组织渗透和多步骤干预来促进糖尿病伤口修复。
