Long-term in vivo biodistribution and toxicity study of functionalized near-infrared persistent luminescence nanoparticles

Xia Sun,Hongwu Zhang,Yi Yang,Junpeng Shi,Xiaoyan Fu

doi:10.1038/s41598-018-29019-z

Abstract

Near-infrared (NIR) persistent luminescence nanoparticles (NPLNPs) have become one of the most promising candidates for bioimaging. Different from the other fluorescence nanoprobes, the NIR persistent luminescence of NPLNPs can last for a long time after excitation, double exposure that is nanoparticles and light exist during the long-term bioimaging. However, to date, the potential risk of nanoparticles and NIR persistent luminescence of NPLNPs is still unknown. In this study, Cr3 + -doped zinc gallate, Zn1.1Ga1.8Sn0.1O4:Cr3+ (ZGO), the most promising NPLNPs in bioimaging, was chosen as a representative for potential risk assessment. We evaluated the potential risk of nanoparticles and NIR persistent luminescence of ZGO for a long period of time. In vitro study showed that the ZGO possessed a low cytotoxicity. In vivo biodistribution results showed that the ZGO mainly accumulated in the reticuloendothelial system after intravenous injection and could be gradually cleared from the body by digestive system. In addition, the ZGO did not exhibit appreciable toxicity in mice over a period of 60 days. It’s also worth mentioning that long-term NIR persistent luminescence of ZGO did not exhibit obvious toxicities both in vitro and in vivo. Our results provide important information with regards to the risk of NPLNPs in long-term bioimaging.

Highlights

In the past few years, optical imaging has received much attention in biomedicine due to its advantages of high sensitivity, non-invasiveness, no radioactivity, and low cost[1,2]
The ZGO was obtained through low temperature calcination at 700 °C for a short time
The results showed that A549, human umbilical vein endothelial cells (HUVEC) and HepG2 cells treated with ZGO at the concentration of 200 μg/mL for 24 h produced a negligible amount of reactive oxygen species (ROS), which had no significant differences in comparison to that of the control (Fig. 3b)

Summary

Introduction

In the past few years, optical imaging has received much attention in biomedicine due to its advantages of high sensitivity, non-invasiveness, no radioactivity, and low cost[1,2]. The phosphor exhibited a long NIR persistent luminescence of more than 1,000 h after excitation by a UV lamp, which has largely solved the drawback of the short persistent luminescence time of the first generation NPLNPs. Using a sol-gel method, LiGa5O8:Cr3+ nanoparticles were synthesized and further applied to ultrasensitive, deep-tissue, and long-term image tracking of cells in vivo[16]. Using a sol-gel method, LiGa5O8:Cr3+ nanoparticles were synthesized and further applied to ultrasensitive, deep-tissue, and long-term image tracking of cells in vivo[16] This generation of NPLNPs still need UV excitation, and it cannot fundamentally solve the drawback of the SNR decrease with the decay of NIR persistent luminescence for in vivo imaging. To determine their potential in vivo risk, we carried out a long-term toxicology analysis of ZGO in mice over a period of 60 days

Methods

Results

Conclusion