title: Renal clearance and degradation of glutathione-coated copper nanoparticles.
abstract: Degradation of inorganic nanoparticles (NPs) into small molecular complexes is often observed in the physiological environment; however, how this process influences renal clearance of inorganic NPs is largely unknown. By systematically comparing renal clearance of degradable luminescent glutathione coated copper NPs (GS-CuNPs) and their dissociated products, Cu(II)-glutathione disulfide (GSSG) complexes (Cu(II)-GSSG), we found that GS-CuNPs were eliminated through the urinary system surprisingly faster and accumulated in the liver much less than their smaller dissociation counterparts. With assistance of radiochemistry and positron emission tomography (PET) imaging, we found that the observed "nano size" effect in enhancing renal clearance is attributed to the fact that GS-CuNPs are more resistant to serum protein adsorption than Cu(II)-GSSG. In addition, since dissociation of GS-CuNPs follows zero-order chemical kinetics, their renal clearance and biodistribution also depend on initial injection doses and their dissociation processes. Quantitative understanding of size effect and other factors involved in renal clearance and biodistribution of degradable inorganic NPs will lay down a foundation for further development of renal-clearable inorganic NPs with minimized nanotoxicity.
authors: †Department of Chemistry, The University of Texas at Dallas, Richardson, Texas 75080, United States.
authors: Shengyang
authors: S
authors: Yang
authors: †Department of Chemistry, The University of Texas at Dallas, Richardson, Texas 75080, United States.
authors: Shasha
authors: S
authors: Sun
authors: †Department of Chemistry, The University of Texas at Dallas, Richardson, Texas 75080, United States.
authors: Chen
authors: C
authors: Zhou
authors: ‡Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
authors: Guiyang
authors: G
authors: Hao
authors: †Department of Chemistry, The University of Texas at Dallas, Richardson, Texas 75080, United States.
authors: Jinbin
authors: J
authors: Liu
authors: ‡Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
authors: Saleh
authors: S
authors: Ramezani
authors: †Department of Chemistry, The University of Texas at Dallas, Richardson, Texas 75080, United States.
authors: Mengxiao
authors: M
authors: Yu
authors: ‡Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
authors: Xiankai
authors: X
authors: Sun
authors: †Department of Chemistry, The University of Texas at Dallas, Richardson, Texas 75080, United States.
authors: Jie
authors: J
authors: Zheng
mesh_terms: D000818:Animals; D003300:Copper / Q000378:metabolism* / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism* / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology*; D053768:Metal Nanoparticles; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D003300:Copper; D005978:Glutathione