Surface charge-dependent mitochondrial response to similar intracellular nanoparticle contents at sublethal dosages

Xiaoting Jin,Qi Wu,Tenglong Cui,Ze Zhang,Haiyi Yu,Guibin Jiang,Guangbo Qu,Jianbo Shi,Xiaolei Liu,Xingchen Zhao,Jie Gao

doi:10.1186/s12989-021-00429-8

Abstract

BackgroundConsidering the inevitability for humans to be frequently exposed to nanoparticles (NPs), understanding the biosafety of NPs is important for rational usage. As an important part of the innate immune system, macrophages are widely distributed in vital tissues and are also a dominant cell type that engulfs particles. Mitochondria are one of the most sensitive organelles when macrophages are exposed to NPs. However, previous studies have mainly reported the mitochondrial response upon high-dose NP treatment. Herein, with gold nanoparticles (AuNPs) as a model, we investigated the mitochondrial alterations induced by NPs at a sublethal concentration.ResultsAt a similar internal exposure dose, different AuNPs showed distinct degrees of effects on mitochondrial alterations, including reduced tubular mitochondria, damaged mitochondria, increased reactive oxygen species, and decreased adenosine triphosphate. Cluster analysis, two-way ANOVA, and multiple linear regression suggested that the surface properties of AuNPs were the dominant determinants of the mitochondrial response. Based on the correlation analysis, the mitochondrial response was increased with the change in zeta potential from negative to positive. The alterations in mitochondrial respiratory chain proteins indicated that complex V was an indicator of the mitochondrial response to low-dose NPs.ConclusionOur current study suggests potential hazards of modified AuNPs on mitochondria even under sublethal dose, indicates the possibility of surface modification in biocompatibility improvement, and provides a new way to better evaluation of nanomaterials biosafety.

Highlights

Nanoparticles (NPs) have been developed for multiple fields, such as textiles, cosmetics, electronics, biomedical applications, and environmental science and technology advances [1, 2]
The hydrodynamic diameters of Gold nanoparticles (AuNPs) detected by DLS were slightly higher than the diameters obtained from TEM (Additional file 1: Fig. S1B), which may be caused by ligand adsorption and electrical double layers on the surface of the AuNPs
Our current study suggested that AuNP exposure at a sublethal dose could contribute to damage to mitochondrial morphology, structure, and function, providing a deeper understanding of mitochondrial alterations upon exposure to AuNPs (Additional file 1: Fig. S11)

Summary

Introduction

Nanoparticles (NPs) have been developed for multiple fields, such as textiles, cosmetics, electronics, biomedical applications, and environmental science and technology advances [1, 2]. The biological effects of NPs are highly determined by their physicochemical properties [5, 6] Among these properties, the diameter of NPs is an important factor influencing the interaction between NPs and biological systems [7]. Gold nanoparticles (AuNPs) with smaller diameter (3 and 6 nm) can enhance the production of proinflammatory cytokines and cause more cytotoxicity than 40 nm [10]. Another important property affecting the nano-bio interface is the surface of nanoparticle properties, which influence the interaction of NPs with biological system, which could lead to different side effects [3, 5, 11]. With gold nanoparticles (AuNPs) as a model, we investigated the mitochondrial alterations induced by NPs at a sublethal concentration

Methods

Results

Conclusion