不同物理化学性质纳米颗粒的血脑屏障通透机制及毒性影响研究进展

如何透过血脑屏障一直是纳米颗粒药物研究的热点和难点。本文查阅了1996年到2015年发表的48篇与纳米颗粒透过血脑屏障相关的重要SCI文献。总结了纳米颗粒透过血脑屏障的不同机制,包括被动扩散、透过细胞间隙和细胞转胞吞等。根据纳米颗粒独特的物理化学性质,详细综述了颗粒大小、表面带电、表面修饰等不同物理化学性质对纳米颗粒透过血脑屏障的影响,以及纳米颗粒对血脑屏障的潜在毒性风险。本文阐释了不同物理化学性质的纳米颗粒如何与血脑屏障相互作用进入大脑,为未来合理设计纳米颗粒,预测其在大脑的分布、生物相互作用和毒性风险提供理论支持。

It remains a challenging task to facilitate nanomedicine to cross the blood-brain barrier in pharmaceutical research.In this paper, we reviewed 48 important SCI papers related with nanoparticles across the blood-brain barrier published from 1996 to 2015.We summarized different mechanisms of nanoparticles across the BBB including diffusion, paracellular pathway, and transcytosis, etc.Then we discussed the influences of nanoparticles with different physicochemical properties(size, surface charge and surface modification)across the BBB which take advantage of physiological properties of the BBB or specific properties.Nanoparticles showed potential to cross the BBB for brain disease treatments.Meanwhile, nanoparticles have potential to lead brain toxicity.The knowledge about the predictive relationships between nanoparticles and their effects on the BBB according to their properties is important for the drug design and risk assessment.Further understanding the nanoparticles modification in the biological system and the interaction with the BBB after the modification will allow us to predict the uptake, biodistribution and bio-interaction of nanoparticles into the brain and the potential toxicity.