title: Short- and Long-Term Tracking of Anionic Ultrasmall Nanoparticles in Kidney.
abstract: While biodistribution of nanoparticles (NPs) has been widely studied at the organ level, relatively little is known about their disposition in organs at the cellular level, especially after long-term exposure. The kidney is regarded as the key organ for the clearance of ultrasmall NPs (<5.5 nm). However, recent studies indicate that NPs in this size range could accumulate in the kidney for extended times without urinary excretion. Using negatively charged quantum dots (QDs) (∼3.7 nm) as a model system, we examined the suborgan disposition of anionic ultrasmall NPs in the kidney at the cellular level after intravenous injection by multiphoton microscopy coupled with fluorescence lifetime imaging. Most of the NPs were initially distributed in the peritubular capillaries or glomerular arterioles after injection, whereas they passed through the fenestrated glomerular endothelium and were gradually taken up by mesangial cells up to 30 days after injection. Only trace amounts of anionic QDs could be detected in the urine, which could be attributed to the barrier of the anionic glomerular basement membrane preventing filtration of anionic QDs. In contrast, cationic QDs of similar size (∼5.67 nm) were found to be readily excreted into urine. This study thus highlights the importance of surface charge in determining renal clearance of ultrasmall NPs. It provides a framework for characterizing and predicting the subcellular disposition in organs and long-term targeting of other NPs, with a physiologically based kinetic model being subsequently developed to describe the suborgan kinetics of anionic ultrasmall NPs.
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland , Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liang
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland , Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia.
authors.forename: Haolu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland , Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia.
authors.forename: Yian
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Faculty of Science and Engineering, Macquarie University , Sydney, NSW 2109, Australia.
authors.forename: Run
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Centre for Education and Research on Ageing and the ANZAC Research Institute, The University of Sydney , Concord Hospital, Concord, NSW 2139, Australia.
authors.forename: Victoria C
authors.initials: VC
authors.lastname: Cogger
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland , Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St. Lucia, QLD 4072, Australia.
authors.forename: Zhi Ping
authors.initials: ZP
authors.lastname: Xu
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland , Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Grice
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland , Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia.|School of Pharmacy and Medical Science, University of South Australia , Adelaide, SA 5001, Australia.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Roberts
mesh_terms: D000818:Animals; D000838:Anions; D002412:Cations; D050533:Glomerular Basement Membrane / Q000187:drug effects* / Q000378:metabolism; D005919:Glomerular Filtration Rate; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D036641:Microscopy, Fluorescence, Multiphoton; D053758:Nanoparticles / Q000378:metabolism*; D061848:Optical Imaging; D010316:Particle Size; D011094:Polyethyleneimine / Q000737:chemistry*; D045663:Quantum Dots / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D055672:Static Electricity; D013870:Thiomalates / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D000838:Anions; D002412:Cations; D013870:Thiomalates; D012710:Serum Albumin, Bovine; D011094:Polyethyleneimine; C046062:2-thiomalic acid
keywords: renal disposition; suborgan kinetics; surface charge; ultrasmall nanoparticles