Glutathione-Mediated Cu(I)/Cu(II) Complexes: Valence-Dependent Effects on Clearance and In Vivo Imaging Application.

Su-Na Yin,Chen Zhou,Shengyang Yang,Yuanyuan Liu

doi:10.3390/nano7060132

Su-Na Yin, Chen Zhou + Show 2 more

Open Access

https://doi.org/10.3390/nano7060132

Copy DOI

Abstract

Contrast imaging agents need to be cleared in a reasonable time (less than 72 h), so it is quite urgent to understand the structure, biocompatibility, and metabolism features of imaging agents. In this work, luminescent Cu(I)-GSH complex and their derivative oxidized Cu(II)-GSSG complex have been easily synthesized. Through systematically probing the renal clearance and biodistribution of the as-prepared copper complexes, we found that Cu(I)-GSH complex revealed much more efficient renal clearance and remarkably lower liver accumulation than that of their oxidation states, which could be due to strong protein binding of partial forms of Cu(II)-GSSG complex. Besides, we also attempted to incorporate radioactive copper-64 into Cu(I)-GSH complex for the synthesis of radioactive contrast agent. Indeed, the as-prepared radioactive Cu(I)-GSH complex also showed consistent high efficiency renal excretion, allowing them to be potential PET imaging agents in clinical translation.

Highlights

The development of contrast agents for bioimaging has aroused great interest in optical imaging, biochemistry, and nanomaterials, due to their vital significance in the early diagnosis of various diseases [1]
We found that the decomposable luminescent silver and copper nanoparticles were able to be eliminated via renal system, different from conventional nanoparticles that were mainly accumulated in the reticuloendothelial system (RES) and other vital organs/tissues [13,14]
Through systematic investigation of the renal elimination and biodistribution of two different complexes, we found that much more (~40%) of the Cu(I)-GSH complex can be excreted from kidney than Cu(II)-GSSG complex in 24 h, their compositions are similar

Summary

Introduction

The development of contrast agents for bioimaging has aroused great interest in optical imaging, biochemistry, and nanomaterials, due to their vital significance in the early diagnosis of various diseases [1]. The US Food and Drug Administration (FDA) has issued warnings on some of contrast probes, which can often induce severe side effects and even organ dysfunction [12] For this reason, the fluorescence contrast agents need favorable biocompatibility, and quick clearance without serious accumulation in organs/tissues after imaging. We found that the decomposable luminescent silver and copper nanoparticles were able to be eliminated via renal system, different from conventional nanoparticles that were mainly accumulated in the RES and other vital organs/tissues [13,14] These examples are the initial studies that demonstrated degradable nanoparticles into complexes could be excreted through kidneys, revealing significant understanding of nanotoxicity and dissociation behavior of inorganic nanoparticles. The quantitative analysis of Cu(I)-GSH and Cu(II)-GSSG complexes in vivo is fundamentally significant for further understanding the valence-dependent renal clearance difference and designing various other renal clearable materials with low toxicity towards clinical translation

Materials

Experimental Animals

Instrumentation

Conclusions