bc5b00003_si_001.pdf (393.34 kB)
Renal Clearance and Degradation of Glutathione-Coated Copper Nanoparticles
journal contribution
posted on 2015-03-18, 00:00 authored by Shengyang Yang, Shasha Sun, Chen Zhou, Guiyang Hao, Jinbin Liu, Saleh Ramezani, Mengxiao Yu, Xiankai Sun, Jie ZhengDegradation 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.