Bioaccumulation and Toxicity of Carbon Nanoparticles Suspension Injection in Intravenously Exposed Mice.

Ping Xie,Xiao-Hai Tang,Tiantian He,Shengnan Yang,Sheng-Tao Yang

doi:10.3390/ijms18122562

Abstract

Carbon nanoparticles suspension injection (CNSI) has been widely used in tumor drainage lymph node mapping, and its new applications in drug delivery, photothermal therapy, and so on have been extensively investigated. To develop new clinical applications, the toxicity of CNSI after intravenous exposure should be thoroughly investigated to ensure its safe use. Herein, we studied the bioaccumulation of CNSI in reticuloendothelial system (RES) organs and the corresponding toxicity to mice. After the intravenous injection of CNSI, no abnormal behavior of mice was observed during the 28-day observation period. The body weight increases were similar among the exposed groups and the control group. The parameters of hematology and serum biochemistry remained nearly unchanged, with very few of them showing significant changes. The low toxicity of CNSI was also reflected by the unchanged histopathological characteristics of these organs. The injection of CNSI did not induce higher apoptosis levels either. The slight oxidative stress was observed in RES organs at high dosages at day 7 post-exposure. The implication to the clinical applications and toxicological evaluations of carbon nanomaterials is discussed.

Highlights

Carbon nanomaterials, such as carbon nanoparticles, carbon quantum dots, fullerene, carbon nanotubes (CNTs), and graphene, have attracted great research interest in the past decades [1,2]
The accumulation and toxicity of Carbon nanoparticles suspension injection (CNSI) were preliminarily evaluated after intravenous injection in mice, where CNSI was trapped in reticuloendothelial system (RES) organs and no apparent toxicity was observed
CNSI accumulated majorly in the liver and spleen after intravenous injection, while only very small amounts were detected in the lungs

Summary

Introduction

Carbon nanomaterials, such as carbon nanoparticles, carbon quantum dots, fullerene, carbon nanotubes (CNTs), and graphene, have attracted great research interest in the past decades [1,2]. More efforts are required to commercialize them, carbon nanomaterials are expected to benefit public health in the future Among these novel carbon nanomaterials, carbon nanoparticles suspension injection (CNSI) is the only one that has been produced on a large scale and applied in clinical treatments. We reported that CNTs accumulated in body during the 90-day observation period and only induced slight toxicity and oxidative stress [21]. Another similar formulation to CNSI was carbon quantum dots (polyethylene glycol (PEG) functionalized carbon nanoparticles), which were nontoxic to mice after intravenous exposure [22]. We systematically investigated the biodistribution and toxicity of CNSI in mice after intravenous injection. The implications to the biosafety evaluations and the new applications of CNSI are discussed

Characterization of CNSI

Toxicity Evaluations

Animal Exposure

Biodistribution of CNSI

Conclusions