众所周知，脑部疾病很难治疗。据物理学家组织网近日报道，约翰·霍普金斯大学研究人员报告称，他们对运载药物的纳米粒子进行了改良，使其能按照预期，安全定量地渗透到脑组织深处。研究人员指出，这一改进在制造灵活药物递送系统、克服脑癌及其他器官疾病障碍方面迈进了一大步。相关论文在线发表于《科学·转化医学》上。
在做完脑肿瘤摘除手术后，标准治疗方案还需要进行化疗，以杀死病灶部位无法手术摘除的残留细胞。但化疗药物剂量很难控制，既要够大才能穿透组织，又要够小才能保证病人安全。这种方法预防肿瘤复发成功率并不高。
为了克服剂量难题，研究小组设计出一种纳米粒子，能在一段时间内持续、稳定地将小剂量药物递送到病灶部位，而且能顺利地一次性就到达大脑，不会被组织环境黏住。约翰·霍普金斯大学病理学家查尔斯·埃伯哈特说，传统的纳米粒子是用像绳子似的分子将药物紧紧缠裹成小球，遇水后缓慢分解，但递送效果并不理想，因为纳米粒子会黏在注射部位的细胞上，不向组织内部移动。
为此，该校化学与生物分子工程研究生、霍普金斯神经外科医生伊丽莎白·南希将聚乙二醇（PEG）涂在大小不同的纳米塑料珠上，稠密的PEG涂层让纳米珠变得更光滑，减小了其与周围环境的相互作用，而且涂层能保护纳米粒子免受机体防御系统攻击。
在组织实验中，他们给涂层纳米珠作了荧光标记，注射进小鼠和人的脑组织切片中，跟踪它们的运动情况，结果发现PEG涂层让较大的纳米珠也能透过组织，有些甚至接近了以往认为的透过脑组织最大限度的2倍。动物实验效果也相同。
随后，他们给一种携带化疗药物紫杉醇的生物降解纳米粒子涂上了PEG。在小鼠脑组织中，没有PEG涂层的纳米粒子运动非常慢，而有涂层的顺利扩散到组织中。南希说，现在纳米粒子能运载的药物量是以前的5倍，在脑组织中的运输距离是以前的3倍。下一步研究将看它们能否减缓动物体内肿瘤的生长。
研究人员指出，他们还希望进一步优化纳米粒子，将其与药物匹配以治疗其他脑部疾病，如多发性硬化症、中风、脑外伤、老年痴呆症和帕金森症等。
A Dense Poly(Ethylene Glycol) Coating Improves Penetration of Large Polymeric Nanoparticles Within Brain Tissue
Elizabeth A. Nance, Graeme F. Woodworth, Kurt A. Sailor, Ting-Yu Shih, Qingguo Xu, Ganesh Swaminathan, Dennis Xiang, Charles Eberhart and Justin Hanes
Prevailing opinion suggests that only substances up to 64 nm in diameter can move at appreciable rates through the brain extracellular space (ECS). This size range is large enough to allow diffusion of signaling molecules, nutrients, and metabolic waste products, but too small to allow efficient penetration of most particulate drug delivery systems and viruses carrying therapeutic genes, thereby limiting effectiveness of many potential therapies. We analyzed the movements of nanoparticles of various diameters and surface coatings within fresh human and rat brain tissue ex vivo and mouse brain in vivo. Nanoparticles as large as 114 nm in diameter diffused within the human and rat brain, but only if they were densely coated with poly(ethylene glycol) (PEG). Using these minimally adhesive PEG-coated particles, we estimated that human brain tissue ECS has some pores larger than 200 nm and that more than one-quarter of all pores are ≥100 nm. These findings were confirmed in vivo in mice, where 40- and 100-nm, but not 200-nm, nanoparticles spread rapidly within brain tissue, only if densely coated with PEG. Similar results were observed in rat brain tissue with paclitaxel-loaded biodegradable nanoparticles of similar size (85 nm) and surface properties. The ability to achieve brain penetration with larger nanoparticles is expected to allow more uniform, longer-lasting, and effective delivery of drugs within the brain, and may find use in the treatment of brain tumors, stroke, neuroinflammation, and other brain diseases where the blood-brain barrier is compromised or where local delivery strategies are feasible.
文献链接：https://stm.sciencemag.org/content/4/149/149ra119.abstract
