Department of Chemistry and Biochemistry, The University of Texas at Dallas, 800 West Campbell Road, Richardson, Texas 75080, USA.
Deparment of Chemistry, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA.
Nat Nanotechnol. 2017 Nov;12(11):1096-1102. doi: 10.1038/nnano.2017.170. Epub 2017 Sep 11.
The glomerular filtration barrier is known as a 'size cutoff' slit, which retains nanoparticles or proteins larger than 6-8 nm in the body and rapidly excretes smaller ones through the kidneys. However, in the sub-nanometre size regime, we have found that this barrier behaves as an atomically precise 'bandpass' filter to significantly slow down renal clearance of few-atom gold nanoclusters (AuNCs) with the same surface ligands but different sizes (Au, Au and Au). Compared to Au (∼1.0 nm), just few-atom decreases in size result in four- to ninefold reductions in renal clearance efficiency in the early elimination stage, because the smaller AuNCs are more readily trapped by the glomerular glycocalyx than larger ones. This unique in vivo nano-bio interaction in the sub-nanometre regime also slows down the extravasation of sub-nanometre AuNCs from normal blood vessels and enhances their passive targeting to cancerous tissues through an enhanced permeability and retention effect. This discovery highlights the size precision in the body's response to nanoparticles and opens a new pathway to develop nanomedicines for many diseases associated with glycocalyx dysfunction.
肾小球滤过屏障被称为“尺寸截止”狭缝,它保留了体内大于 6-8nm 的纳米颗粒或蛋白质,并通过肾脏迅速排泄较小的颗粒。然而,在亚纳米尺寸范围内,我们发现这个屏障表现为一种原子精确的“带通”滤波器,显著减缓了具有相同表面配体但尺寸不同(Au、Au 和 Au)的少数原子金纳米团簇(AuNCs)的肾脏清除率。与 Au(约 1.0nm)相比,仅少数原子的尺寸减少就会导致早期消除阶段肾脏清除效率降低四至九倍,因为较小的 AuNCs比较大的 AuNCs更容易被肾小球糖萼捕获。这种亚纳米范围内独特的体内纳米生物相互作用也减缓了亚纳米 AuNCs 从正常血管外渗的速度,并通过增强通透性和保留效应增强了它们对癌组织的被动靶向性。这一发现强调了纳米颗粒在体内响应中的尺寸精度,并为开发与糖萼功能障碍相关的许多疾病的纳米药物开辟了新途径。