新型自驱动阴阳型纳米马达用于跨血脑屏障

Most of the drugs cannot enter into brain to have further therapeutic effect because of the existence of blood-brain barrier, which restrain the drugs to be applied in the treatment of central nervous system diseases. Recently, nanocarriers were often used to facilitate the uptake of drugs into brain tissues, making it possible for the treatment of brain diseases. However, traditional nanocarriers without self-driving force had quite some limitations. In this project, we want to design a self-propelled nanomotor system based on biocompatible and fully bioavailable glucose fuel for crossing the blood-brain barrier. Cascade reactions between glucose oxidase and catalase were introduced onto the surface of Janus nanoparticles, which can degrade the substrate glucose step by step, leading to the autonomous movement of nanomotors. Different with traditional nanocarriers with thermodynamic equilibrium and Brownian motion behavior, nanomotor can move autonomously and enhance the collision toward cells. The induced collision force can further facilitate the cellular endocytosis of nanomotors, therefore nanomotors are possible to cross the blood-brain barrier to achieve therapnostics for brain diseases. As a result of systemic study of cellular level (in vitro) to explore the transport efficacy and the mechanism of nanomotor, we want to develop a novel self-propelled nanomotor system with high blood-brain barrier crossing efficiency.

血脑屏障的存在使得大多数的药物难以进入脑组织进而发挥药效，这极大地限制了药物在中枢神经系统疾病中的应用。近年来，纳米载体常用来促进药物的脑摄入，为实现脑部疾病的治疗提供了可能，然而传统的纳米载体没有动力来源，因此具有一定的局限性。本项目旨在构建一类以生物相容且生物体内所富含的物质葡萄糖为燃料的自驱动纳米马达系统用于血脑屏障的跨越。通过在阴阳型纳米粒表面引入葡萄糖氧化酶-过氧化氢酶级联反应体系，完成对底物葡萄糖的逐步分解，从而实现纳米马达的自主运动。与传统的处于热力学平衡态、只进行布朗运动的纳米载体不同的是，纳米马达在溶液中的自主运动能够增强其对细胞的碰撞，而碰撞所产生的撞击力可以进一步促进细胞对其的内吞，从而有望跨越血脑屏障，实现脑部疾病的诊断与治疗。本项目力求通过体外细胞水平上的研究，探索纳米马达跨血脑屏障的转运能力以及转运机制，以期得到具有高效跨越血脑屏障能力的新型自驱动纳米马达系统。

血脑屏障的存在使得大多数的药物难以进入脑组织进而发挥药效，这极大地限制了药物在脑部疾病中的应用。近年来，纳米载体常用来促进药物的脑摄入，为实现脑部疾病的治疗提供了可能，然而传统的纳米载体没有动力来源，因此具有一定的局限性。针对这一问题，本项目通过对镁微球进行不对称修饰制备得到具有阴阳型结构的自驱动微米马达用于脑卒中的主动氢气治疗。作为还原性气体，镁与水反应生成的氢气不仅能推动镁基马达的运动，而且还能够特异性地清除具有高细胞毒性的活性氧。通过脑立体定向仪将镁基马达精确地注射到目标区域，利用马达产生氢气的抗氧化、抗炎作用来减轻脑缺血再灌注损伤，从而实现急性缺血性脑中风的精准治疗。此外，本项目还首次构建了DNA酶驱动的纳米马达体系，该马达可以由极低水平的底物DNA提供驱动力。该马达对DNA丰富的区域表现出显著的趋化行为，这一点与包括肿瘤在内的许多疾病具有很好的生理相关性。在有凋亡肿瘤细胞所产生的DNA梯度情况下，纳米马达能够感知细胞所释放的DNA信号，并表现出趋向于肿瘤细胞的靶向运动行为。该马达具有自导航和自靶向的趋化运动能力，有望在未来实现脑部肿瘤的诊断和治疗。