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

Abstract

The glomerular filtration barrier is known as a “size cut-off” slit to retain nanoparticles or proteins larger than 6~8 nm in the body, and to rapidly excrete the smaller ones through the kidneys. However, in a sub-nm size regime, we found that this barrier behaved 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 resulted in 4~9 times reductions in the renal clearance efficiency in the early elimination stage because the smaller AuNCs were more readily trapped by the glomerular glycocalyx than the larger ones. This 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 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.

Micelle-Forming Dexamethasone Prodrug Attenuates Nephritis in Lupus-Prone Mice without Apparent Glucocorticoid Side Effects

“…56 We postulate that the proposed mechanism of physical retention of AuNCs by the glycocalyx of the glomeruli may have also helped to slow down the clearance of ZSJ-0228 from the kidney and thus contributed to its high kidney distribution. (2) According to the ELVIS mechanism, inflammatory cells’ accelerated sequestration is one of the major contributors to the high retention of nanomedicine in inflammatory tissues.…”

Carbon Dots as a New Class of Diamagnetic Chemical Exchange Saturation Transfer (diaCEST) MRI Contrast Agents

“…[34] Considering their favorable size and biocompatibility,Cdots are promising diaCEST contrast agents for awide array of biomedical applications,f or example,t umor screening or even theranostics by cancer cell [35] -o rt umor vasculature [36] specific markers.H owever, there are still af ew technical considerations towards potential future studies.F irstly,g iven the presence of abundant in vivo endogenous proteins and metabolites whose CEST contrasts fall in the frequency range of 0-4 ppm, [16b] specificity of AC-dots (approximately 2ppm) is relatively inefficient. [37] Taken together,weforesee avast potential for the C-dots to be used as anew group of CEST MRI contrast agents. Apost-synthetic surface modification would be av iable option, which is currently under investigation.…”

Light-responsive nanomedicine for biophotonic imaging and targeted therapy

“…Then, controlled conjugation of the remaining amines with succinic anhydride or acetic anhydride resulted in CDPLs with positive, zwitterionic, negative, or non-charges. Their size was purposely designed to be smaller than 5.5 nm to promote rapid renal clearance from the kidneys to the bladder [36,62,77,78]. This represents a totally different approach to the traditional targeting strategy of NPs over 100 nm which was based on long blood circulation and the EPR effect for passive targeting [8,9].…”

“…Renal clearable ultrasmall gold NPs can be used for passive tumor targeting based on their rapid biodistribution and sustained retention at the tumor microenvironment. Especially, gold NPs are advantageous for quantification of renal transport kinetics and tumor targeting when combined with NIR and X-ray imaging modality [77]. Indeed, selective delivery of nanomedicine to the tumor site is vital to minimizing the potential toxicity of NPs and expediting their clinical translation [11].…”