2012年9月2日 訊 /生物谷BIOON/ --運(yùn)用納米粒在大腦中進(jìn)行治療通常都會遇到一種并不算好的結(jié)果,，理論上來講,，這種小的納米粒子可以運(yùn)輸特殊的治療藥物至腦瘤部位來發(fā)揮殺滅癌細(xì)胞的作用，但是攜帶藥物的納米粒子在大腦細(xì)胞狹窄和糖漿狀的空間中進(jìn)行穿梭確實(shí)非常困難,，那么此過程中少量的潤滑作用或許會幫助納米粒子成功運(yùn)輸藥物至癌細(xì)胞部位,。
來自約翰霍普金斯大學(xué)的研究者如今發(fā)現(xiàn)了腦組織如何使其對于納米粒子變得不通透，研究者表示，大腦腦組織含有極具粘性的漿液組織,，就好比是粘液具有強(qiáng)的粘著性一樣,，其可以保護(hù)機(jī)體免于傷害，比如呼吸系統(tǒng)就可以通過粘附外源顆粒來保護(hù)機(jī)體,。腦組織的粘附性可以限制外源顆粒的尺寸,，使其緩慢通過腦部。直徑在64nm以下的信號分子,，營養(yǎng)物質(zhì)和廢棄物可以相對輕松地通過腦組織,，但是攜帶藥物的大一點(diǎn)的納米粒便會被攔截下來。
研究者Hanes和其同事加大了腦組織對于尺寸的限制,，其通過給納米粒套上一層填充高聚體分子的外套,，這種外套可以通過避免靜電以及和周圍組織的疏水作用來潤滑納米粒，而且也可以避免其吸附于細(xì)胞上,。使用此種方法,，研究者可以觀察到直徑為114nm的納米粒穿過小鼠、大鼠以及人類的腦組織,。
研究者表示后續(xù)研究需要繼續(xù)開展,，他們希望研究發(fā)現(xiàn)當(dāng)納米粒結(jié)合了治療藥物后，這些顆粒是否可以通過任何一個靶點(diǎn)來發(fā)揮作用,，而且納米粒進(jìn)入機(jī)體后不會引發(fā)任何副作用,。相關(guān)研究成果刊登在了近日的國際雜志Science Translational Medicine上。（生物谷Bioon.com）
編譯自：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.
