The glomerular filtration barrier is known as a “size cut-off” 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-nm 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 the 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. The unique in vivo nano-bio interaction in the sub-nm regime also slows down the extravasation of sub-nm 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.

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

256th National Meeting (2018)

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