Abstract

The rapid development of nanotechnologies is raising safety concerns because of the potential effects of engineered nanomaterials on human health, particularly at the respiratory level. Since the last decades, many in vivo studies have been interested in the pulmonary effects of different classes of nanomaterials. It has been shown that some of them can induce toxic effects, essentially depending on their physico-chemical characteristics, but other studies did not identify such effects. Inflammation and oxidative stress are currently the two main mechanisms described to explain the observed toxicity. However, the exact underlying mechanism(s) still remain(s) unknown and autophagy could represent an interesting candidate. Autophagy is a physiological process in which cytoplasmic components are digested via a lysosomal pathway. It has been shown that autophagy is involved in the pathogenesis and the progression of human diseases, and is able to modulate the oxidative stress and pro-inflammatory responses. A growing amount of literature suggests that a link between nanomaterial toxicity and autophagy impairment could exist. In this review, we will first summarize what is known about the respiratory effects of nanomaterials and we will then discuss the possible involvement of autophagy in this toxicity. This review should help understand why autophagy impairment could be taken as a promising candidate to fully understand nanomaterials toxicity.

Highlights

  • Nanotechnologies represent a major technological advance of this last century

  • We will go through the actual knowledge available in the literature regarding the pulmonary toxicity of nanomaterials, and will discuss on autophagy as a novel mechanism possibly underlying this toxicity

  • Because autophagy is a dynamic process, there is an essential need to measure the autophagic flux; the assessment of the number of autophagosomes alone is not enough to conclude about the efficiency of autophagy

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Summary

Introduction

Nanotechnologies represent a major technological advance of this last century. Their objects are engineered nanomaterials (at least one dimension in the nanometer range) which possess astonishing physical and chemical properties. Questions raise regarding the potential (human and environmental) toxicity of these nanomaterials, at the respiratory level. These questions are justified by the knowledge of the toxic effects of micrometric particles from atmospheric pollution on human health, and the fear to get an amplification of these effects because of the (nano) size of the materials blamed. We will go through the actual knowledge available in the literature regarding the pulmonary toxicity of nanomaterials, and will discuss on autophagy as a novel mechanism possibly underlying this toxicity

Pulmonary Toxicity of Nanomaterials
Lung Remodeling Manifestations
Underlying Biological Mechanisms
Oxidative Stress
Inflammation
Genotoxicity
Interaction with the Protein Corona
Physico-Chemical Determinants
Autophagy
Autophagy Machinery
Initiation
Autophagosome Formation and Elongation
Evaluation of Autophagic Activity
Autophagy in Physiological and Pathological Conditions
Autophagy and Lung Diseases
Autophagy and Cancer
Evidences of Autophagy Perturbation by Nanomaterials
Mechanisms of Autophagy Perturbation by Nanomaterials
Conclusions
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