Autophagy as new emerging cellular effect of nanomaterials

Abstract

The biosafety issue of nanoscale materials is getting more and more attention with their increasing manufacture and application. In the research of cellular effects and underlying mechanisms related to toxicity of nanomaterials, most emphasis were placed on processes such as apoptosis, metabolic inhibition and oxidative stress. Recent evidence suggests that autophagy is part of the biological effects by nanomaterials and various kinds of nanomaterials are capable of disturbing the autophagic process. This review will highlight the importance of autophagy as an emerging mechanism of nanomaterial toxicity and the implication in the therapy of autophagy-related diseases. We summarize current research status of interaction between nanomaterials and autophagic pathways. It is of note that nanomaterials can either induce or block autophagy, which result in similar phenotype but completely different biological consequence. It is therefore important to perform comprehensive analysis of the whole autophagic flux in the future research. Nanomaterials refer to materials with the size range between 1 and 100 nanometers in one or more dimensions [1]. Due to their superior physicochemical properties, such as ultra small size, increased ratio of surface area to volume, multiple options for modification and relatively good biocompatibilities, application of nanomaterials in research as well as in industry becomes more and more common. It is predicted that the total amount of nanomaterials' production will increase up to 58000 tons by 2020. Particularly, the utilization of nanomaterials in biomedical research as biosensors, drug-carriers, or imaging agents was extensively studied [2][3][4]. Large scaled preparation and application of nanomaterials increase their possibilities to be exposed to human beings or enter the environment [5][6][7]. Therefore the impact of nanomaterials on environment and human health has attracted high attention. Related studies were carried out on the biological effect of various kinds of nanomaterials both in vitro and in vivo [8]. To date, reported physiological changes of a cell or an organism that exposed to nanomaterials include: reactive oxygen species (ROS)-related pathological responses (such as damaged membrane, mitochondrial damage and necrosis), apoptosis, inflammation and altered differentiation patterns, etc [9][10][11][12]. Recently, autophagy as an essential cellular process and a novel biological effect of nanomaterials on eukaryotes, has received much attention. Many nanomaterials were reported to be able to change the basal level of autophagy [13,14]. Autophagy can crosstalk with other cellular process, such as apoptosis and necrosis, and therefore is an important part of the cellular effect of nanomaterials [15,16]. Moreover, nanomaterials-induced autophagy showed potential for the treatment of certain diseases including neurodegenerative diseases and cancer [13,17]. Hence, in this review we summarize the current research on the effect of various kinds of nanomaterials on autophagy. ...

Necrotic, apoptotic and autophagic cell fates triggered by nanoparticles

“…However, other stressful factors that trigger autophagy such as cell membrane damage, and ROS production must be evaluated to give more information on the mechanism. After the characterization of NPs and evaluation of some eventual risk factors, to track autophagy, autophagosomes as double-membrane vesicles might be monitored via electron microscopy [250].…”

“…Autophagy has a close crosstalk with other cell death and signaling pathways; thus, cellular outcomes induced by autophagic NPs are very complex [250]. Although NPs primarily induce macroautophagy, based on the increased formation of and detection of NPs within autophagosomes, it is difficult to classify autophagic effects of NPs as a cell death mechanism at first glance [4,250,254]. In most cases, cells respond to NPs as an endosomal pathogen; the NPs are ubiquitinated leading to sequestration by a phagophore.…”

“…However, fullerene at nanocytotoxic concentration may induce autophagy and increase the killing potential of chemotherapeutics, and even may be influential in treatment of neurodegenrative disorders. In fact, the effects of NPs show two-fold behavior based on concentration-they may either disrupt autophagy or induce auto-phagy [250].…”

“…However, this NP is considered as a candidate in anti-tumor therapy due to its being scavenged as an antigen by T cells, so that less antigen is needed overall to provoke adequate T cell production [246]. Similarly, Ag nanowire, manganese NPs, neodymium(III) oxide (Nd 2 O 3 ), samarium oxide, europium oxide, gadolinium oxide, cerium dioxide, lanthanum oxide and terbium oxide NPs also induce autophagy [250].…”

In vitro and in vivo cytocompatibility evaluation of biodegradable magnesium-based stents: a review

“…At present, there are two methods to reduce the degradation rate and improve their mechanical properties. One is alloying with elements such as calcium, zinc, strontium, zirconium, rare earth elements, and aluminum [13,20,21], and another is surface modification [22][23][24]. Both in vitro and in vivo evaluations must be carried out to verify the feasibility of Mg-based stents before the application in human.…”