Role for nanomaterial-autophagy interaction in neurodegenerative disease. Autophagy 4:1097-1100

Nanotechnology Characterization Laboratory, Advanced Technology Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland 21702, USA.
Autophagy (Impact Factor: 11.75). 12/2008; 4(8):1097-100. DOI: 10.4161/auto.7142
Source: PubMed


Nanotechnology is the control and manipulation of materials in the size range of 1-100 nm. Due to increasing research into the potential beneficial applications of nanotechnology, there is an urgent need for the study of possible health risks. Several researchers, including those in our laboratory, have demonstrated elevated levels of autophagic vacuoles upon exposure of cells to certain nanomaterials, including carbon- and metal-based nanoparticles. While this apparent increase in autophagic activity may be an appropriate cellular response toward nanomaterial clearance, often the interaction between nanomaterials and the autophagy pathway is disruptive, resulting in severe morphological changes and coincident cell death. Interestingly, epidemiological studies have identified an association between exposure to combustion-derived ambient particles (which are predominantly nanoscale) and neurological conditions with Alzheimer's and Parkinson's disease-like pathologies. Becuse impaired autophagy may play an important role in the pathogenesis of these and other diseases, it is intriguing to speculate about the plausible involvement of nanoscale particulates in this process. The interaction of nanomaterials with the autophagy pathway, and the potential negative consequences of resulting autophagy dysfunction, should be explored further.

Full-text preview

Available from:
  • Source
    • "It has been reported that some nanoparticles such as nanoscale carbon black, fullerene, nanoscale neodymium oxide could induce autophagic cell death [16]. On the other hand, nanomaterials such as fullerene derivative may impede autophagy by causing lysosomal disorders, such as lysosome localization and enzyme inhibiting [17]. Autophagy functions as a tumor suppression mechanism by removing damaged organelles/proteins and limiting cell growth and genomic instability [18] [19]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Nanoparticles of biodegradable polymers (NPs) have been widely used for drug delivery. However, there has been little research on their fate after internalized into the cells. We show in this research by using docetaxel as a model anticancer drug, which is formulated in the cholic acid conjugated nanoparticles of poly(lactic-co-glycolic acid (PLGA NPs) that the NPs induce autophagy of the cancer cells and thus may hinder the advantages of the nanomedicine. Moreover, we show both in vitro and in vivo that co-administration of autophagy inhibitors such as 3-methyladenine (3-MA) and Chloroquine (CQ) could greatly enhance the therapeutic effects of the nanoparticle formulation. The IC50 values of the drug formulated in the PLGA NPs after 24 h treatment with no autophagy inhibitor or in combination with 10 mm 3-MA or 30 μm CQ are 38.27 ± 1.23, 6.7 ± 1.05, 4.78 ± 1.75 μg/mL, which implie 5.7 or 8,0 fold efficient by the autophagy inhibition respectively. Moreover, both the volume and the weight of the shrunk tumor of the mice after 20 day treatment with the PLGA NPs formulation combined with 3-MA or CQ are found to be only about a half in comparison with the treatment with the PLGA NPs formulation alone. In this research, we reported such a new mechanism of cancer cells to have PLGA NPs captured and degraded by auto-lysosomes. The findings provide advanced knowledge for development of nanomedicine for clinical application.
    Full-text · Article · Dec 2013 · Biomaterials
  • Source
    • "In searching for new emerging mechanisms of action of NM toxicity, recent literature data strongly highlight the roles of autophagy and lysosomal dysfunction [58]. Most likely, autophagy induction may be used to degrade NMs, perceived by the cell as foreign body, via sequestration into autophagosomes [59]. Several papers suggest that this interaction could be exploited in cancer management. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Autophagy represents a cell's response to stress. It is an evolutionarily conserved process with diversified roles. Indeed, it controls intracellular homeostasis by degradation and/or recycling intracellular metabolic material, supplies energy, provides nutrients, eliminates cytotoxic materials and damaged proteins and organelles. Moreover, autophagy is involved in several diseases. Recent evidences support a relationship between several classes of nanomaterials and autophagy perturbation, both induction and blockade, in many biological models. In fact, the autophagic mechanism represents a common cellular response to nanomaterials. On the other hand, the dynamic nature of autophagy in cancer biology is an intriguing approach for cancer therapeutics, since during tumour development and therapy, autophagy has been reported to trigger both an early cell survival and a late cell death. The use of nanomaterials in cancer treatment to deliver chemotherapeutic drugs and target tumours is well known. Recently, autophagy modulation mediated by nanomaterials has become an appealing notion in nanomedicine therapeutics, since it can be exploited as adjuvant in chemotherapy or in the development of cancer vaccines or as a potential anti-cancer agent. Herein, we summarize the effects of nanomaterials on autophagic processes in cancer, also considering the therapeutic outcome of synergism between nanomaterials and autophagy to improve existing cancer therapies.
    Full-text · Article · Mar 2013 · Cancers
  • Source
    • "Disruption in autophagosome trafficking to the lysosome has also been implicated in neurodegenerative diseases, such as mutant dynactin associated motor neuron disease and amyotrophic lateral sclerosis, as well as myopathies, such as inclusion body myopathy [33]. As exposure to airborne pollution has been associated with Alzheimer and Parkinson-like pathologies, and nanoparticles are the primary particle number and surface area component of pollution-derived particulates, we (S.T.S.) have recently postulated a relationship between nanoparticle-induced autophagy dysfunction and pollution-associated neurodegeneration [2]. In support of this hypothesis, autophagy dysfunction has recently been postulated as a mechanism of manganese nanoparticle-induced cytotoxicity in dopaminergic neuronal cells [79]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The study of the potential risks associated with the manufacture, use, and disposal of nanoscale materials, and their mechanisms of toxicity, is important for the continued advancement of nanotechnology. Currently, the most widely accepted paradigms of nanomaterial toxicity are oxidative stress and inflammation, but the underlying mechanisms are poorly defined. This review will highlight the significance of autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity. Most endocytic routes of nanomaterial cell uptake converge upon the lysosome, making the lysosomal compartment the most common intracellular site of nanoparticle sequestration and degradation. In addition to the endo-lysosomal pathway, recent evidence suggests that some nanomaterials can also induce autophagy. Among the many physiological functions, the lysosome, by way of the autophagy (macroautophagy) pathway, degrades intracellular pathogens, and damaged organelles and proteins. Thus, autophagy induction by nanoparticles may be an attempt to degrade what is perceived by the cell as foreign or aberrant. While the autophagy and endo-lysosomal pathways have the potential to influence the disposition of nanomaterials, there is also a growing body of literature suggesting that biopersistent nanomaterials can, in turn, negatively impact these pathways. Indeed, there is ample evidence that biopersistent nanomaterials can cause autophagy and lysosomal dysfunctions resulting in toxicological consequences.
    Full-text · Article · Jun 2012 · Particle and Fibre Toxicology
Show more