2012年9月2日 讯 /生物谷BIOON/ --运用纳米粒在大脑中进行治疗通常都会遇到一种并不算好的结果，理论上来讲，这种小的纳米粒子可以运输特殊的治疗药物至脑瘤部位来发挥杀灭癌细胞的作用，但是携带药物的纳米粒子在大脑细胞狭窄和糖浆状的空间中进行穿梭确实非常困难，那么此过程中少量的润滑作用或许会帮助纳米粒子成功运输药物至癌细胞部位。
来自约翰霍普金斯大学的研究者如今发现了脑组织如何使其对于纳米粒子变得不通透，研究者表示，大脑脑组织含有极具粘性的浆液组织，就好比是粘液具有强的粘着性一样，其可以保护机体免于伤害，比如呼吸系统就可以通过粘附外源颗粒来保护机体。脑组织的粘附性可以限制外源颗粒的尺寸，使其缓慢通过脑部。直径在64nm以下的信号分子，营养物质和废弃物可以相对轻松地通过脑组织，但是携带药物的大一点的纳米粒便会被拦截下来。
研究者Hanes和其同事加大了脑组织对于尺寸的限制，其通过给纳米粒套上一层填充高聚体分子的外套，这种外套可以通过避免静电以及和周围组织的疏水作用来润滑纳米粒，而且也可以避免其吸附于细胞上。使用此种方法，研究者可以观察到直径为114nm的纳米粒穿过小鼠、大鼠以及人类的脑组织。
研究者表示后续研究需要继续开展，他们希望研究发现当纳米粒结合了治疗药物后，这些颗粒是否可以通过任何一个靶点来发挥作用，而且纳米粒进入机体后不会引发任何副作用。相关研究成果刊登在了近日的国际杂志Science Translational Medicine上。（生物谷Bioon.com）
编译自：Lubricated nanoparticles penetrate the brain
doi:10.1126/scitranslmed.3003594
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PMID:
A Dense Poly(Ethylene Glycol) Coating Improves Penetration of Large Polymeric Nanoparticles Within Brain Tissue
Elizabeth A. Nance1,2,*, Graeme F. Woodworth1,3,*, Kurt A. Sailor4, Ting-Yu Shih2, Qingguo Xu1,5, Ganesh Swaminathan2, Dennis Xiang2, Charles Eberhart1,5,6 and Justin Hanes1,2,3,5,†
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.
