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Glomerular barrier behaves as an atomically precise bandpass filter in a sub-nanometre regime

Nature Nanotechnology volume 12, pages 1096–1102 (2017)Cite this article

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Abstract

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 (Au18, Au15 and Au10-11). Compared to Au25 (∼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.

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Figure 1: Renal clearance of different sized AuNCs and schematic diagram of the glomerular filtration membrane.
Figure 2: EM images of the ultrastructure of the glomerular filtration membrane from mice after i.v. injection of PBS, Au25 or Au18.
Figure 3: In vivo behaviour of few-atom AuNCs.
Figure 4: Tumour targeting efficiency and long-term accumulation in the body.

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Acknowledgements

This study was in part supported by the NIH (1R01DK103363), CPRIT (RP140544) and a start-up fund from the University of Texas at Dallas (to J.Z.).

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, The University of Texas at Dallas, 800 West Campbell Road, Richardson, 75080, Texas, USA

    Bujie Du, Xingya Jiang, Qinhan Zhou, Mengxiao Yu & Jie Zheng

  2. Deparment of Chemistry, Carnegie Mellon University, Pittsburgh, 15213, Pennsylvania, USA

    Anindita Das & Rongchao Jin

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  1. Bujie Du
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  4. Qinhan Zhou
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Contributions

J.Z. conceived the idea and designed experiments with B.D. and R.J. B.D. performed in vivo experiments and analysed data with J.Z. X.J., Q.Z. and A.D. synthesized AuNCs. X.J. and M.Y. assisted with the in vivo experiment. J.Z. and B.D. wrote the manuscript. J.Z. supervised the project. All authors discussed the results and commented on the manuscript.

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Correspondence to Jie Zheng.

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Du, B., Jiang, X., Das, A. et al. Glomerular barrier behaves as an atomically precise bandpass filter in a sub-nanometre regime. Nature Nanotech 12, 1096–1102 (2017). https://doi.org/10.1038/nnano.2017.170

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