Nanomaterials and hepatic disease: toxicokinetics, disease types, intrinsic mechanisms, liver susceptibility, and influencing factors

Ting Sun,Yiyuan Kang,Lingling Ou,Jia Liu,Xiangning Liu,Renfa Lai,Longquan Shao,Yanli Zhang

doi:10.1186/s12951-021-00843-2

Ting Sun, Yiyuan Kang + Show 6 more

Open Access

https://doi.org/10.1186/s12951-021-00843-2

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Abstract

The widespread use of nanomaterials (NMs) has raised concerns that exposure to them may introduce potential risks to the human body and environment. The liver is the main target organ for NMs. Hepatotoxic effects caused by NMs have been observed in recent studies but have not been linked to liver disease, and the intrinsic mechanisms are poorly elucidated. Additionally, NMs exhibit varied toxicokinetics and induce enhanced toxic effects in susceptible livers; however, thus far, this issue has not been thoroughly reviewed. This review provides an overview of the toxicokinetics of NMs. We highlight the possibility that NMs induce hepatic diseases, including nonalcoholic steatohepatitis (NASH), fibrosis, liver cancer, and metabolic disorders, and explore the underlying intrinsic mechanisms. Additionally, NM toxicokinetics and the potential induced risks in the livers of susceptible individuals, including subjects with liver disease, obese individuals, aging individuals and individuals of both sexes, are summarized. To understand how NM type affect their toxicity, the influences of the physicochemical and morphological (PCM) properties of NMs on their toxicokinetics and toxicity are also explored. This review provides guidance for further toxicological studies on NMs and will be important for the further development of NMs for applications in various fields.

Highlights

With the development of nanotechnology, nanomaterials (NMs) are increasingly being used in various industrial, agricultural and commercial applications—e.g., as additives in food, sunscreens, cosmetics, pharmaceutical products, agricultural products and diesel fuel [1–3]
Liver impairments—e.g., oxidative stress, inflammatory stress, liver dysfunction, DNA damage, steatosis, fibrosis, and cell death—caused by NMs have been observed in numerous studies [5–8]
This review discusses possible NMinduced liver diseases and the intrinsic mechanisms based on the current understanding of NM toxicokinetics and considers the contribution of potential susceptibility factors to provide guidelines for the biosafety of NMs

Summary

Introduction

With the development of nanotechnology, nanomaterials (NMs) are increasingly being used in various industrial, agricultural and commercial applications—e.g., as additives in food, sunscreens, cosmetics, pharmaceutical products, agricultural products and diesel fuel [1–3]. Based on the evidence above, we postulate that NMs induce HSC activation by stimulating TGF-β/SMAD-dependent and -independent signaling, leading to liver fibrosis.

Results

Conclusion