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WIREs Nanomed Nanobiotechnol
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Renal clearable noble metal nanoparticles: photoluminescence, elimination, and biomedical applications

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Metal nanoparticles have demonstrated broad and promising biomedical applications in research laboratories, but how to fulfill their promises in the clinical practices demands extensive effort to minimize their non‐specific accumulation in the body. In the past 6 years, we have developed a class of renal clearable noble metal nanoparticles with tunable visible and near‐infrared emission, which can behave like small molecular contrast agents to be effectively eliminated through the kidneys. By taking advantage of the unique clearance pathway, we were able to gain some fundamental understanding of how engineering nanoparticles cleared out of the body through urinary system. Moreover, they also provided unique opportunities in early cancer detection and kidney functional imaging that were often challenging to be achieved with non‐renal clearable nanoparticles and small molecular probes. In this review, we summarize key factors that govern in the renal clearance of luminescent noble metal nanoparticles and their strengths in cancer targeting and kidney functional imaging. At the end, we also outline several key challenges that need to be addressed before they can be considered in the clinical practices. WIREs Nanomed Nanobiotechnol 2017, 9:e1453. doi: 10.1002/wnan.1453 This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
Schematic illustration of the formation of ~2 nm luminescent GS‐AuNPs from dissociation process of polymeric gold thiolates (Au‐SR).
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Schematic illustration of GS‐AuNPs conjugated with insulin. (Reprinted with permission from Ref . Copyright 2015 American Chemical Society)
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(a) Noninvasive fluorescence images of mice at different time points post‐injection of GS‐AuNPs. (b), (c) Time‐fluorescence intensity curves of kidneys in the sham control group and the unilateral ureteral obstruction (UUO) model. (*) Percentage of relative renal function (%RRF = [peak value of LK or RK/(peak value of LK + peak value of RK)] × 100%), (**) clearance percentage at 60 min = [(peak value‐intensity at 60 min)/peak value] × 100%. (Reprinted with permission from Ref . Copyright 2015 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)
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(a) The relationship between area under the curve (AUC) and particle core density. (b) Fitted linear relationship between tumor accumulation and particle core density. (Reprinted with permission from Ref . Copyright 2016 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)
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(a) In vivo near‐infrared fluorescence images of the mouse intravenously injected (i.v.) with PEG‐AuNPs at 5, 12, 18, 24, and 48 h p.i. (b) Time‐dependent contrast index of the tumor area after i.v. of the PEG‐AuNPs or GS‐AuNPs. (c) Accumulation and retention kinetics of the PEG‐AuNPs in tumor and normal tissues. (Reprinted with permission from Ref . Copyright 2013 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim) (d) Tumor targeting efficiencies of representative non‐renal clearable inorganic nanoparticles (NPs) and renal clearable inorganic NPs following i.v. (Reprinted with permission from Ref . Copyright 2015 American Chemical Society)
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(a) Renal clearance profiles of four metal nanoparticles (NPs) within 48 h after intravenous injection. (b) The exponential decay of 2‐h renal clearance as particle core density decreases. (Reprinted with permission from Ref . Copyright 2016 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)
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(a) Renal clearance profiles (inset: PEG‐AuNPs in urine measured by inductively coupled plasma mass spectrometry at 12 and 24 h p.i.) and (b) pharmacokinetics of PEG‐AuNPs and GS‐AuNPs after intravenous injection. (Reprinted with permission from Ref . Copyright 2013 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)
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(a) Glomerular filtration is a nanoscale phenomenon. The glomerular capillary wall is made of three specialized layers: fenestrated endothelium, glomerular basement membrane, and podocyte extensions of glomerular epithelial cells. (Reprinted with permission from Ref . Copyright 2013 Elsevier) (b) Fitted exponential (R2 = 0.995) relationship between the HD of different GS‐AuNPs and the amount ratio accumulated in urine/liver. (Reprinted with permission from Ref . Copyright 2011 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)
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(a) Hypothesized two distinct local Au bonding environments of 600 and 810 nm‐emitting GS‐AuNPs. (b), (c) Absorption, excitation, and emission spectra of 600 and 810 nm‐emitting GS‐AuNPs. (d), (e) Transmission electron microscopy images and size analysis of 600 and 810 nm‐emitting GS‐AuNPs. (Reprinted with permission from Ref . Copyright 2016 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)
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