Interplay of oxidative stress and autophagy in pamam. Tio 2 nanoparticles nps could promote the reactive oxygen species ros. Rapamycin nanoparticles target defective autophagy in muscular dystrophy to enhance both strength and cardiac function. Application note detection of autophagy using automated imaging. The eukaryotic endomembrane system is a complex series of interconnected membranous organelles that play important roles in responding to stress and maintaining cell homeostasis during health and disease.
Thus, autophagy induction by nanoparticles may be an attempt to degrade what is perceived by the cell as foreign or aberrant. Autophagy induction is a common outcome also in cancer pdt and occurs in a variety of cell lines photosensitized with a broad spectrum of pss. In particular, the cellular response to nanomaterials is mediated by the lysosomeautophagy system, which is the main catabolic pathway in mammalian cells that mediates degradation of a variety of nano sized materials that are encountered by the cell through the lysosome. Autophagy pathway has been considered well to be involved in numerous human diseases from inflammatory disease to cancer, and accordingly, lots of autophagy regulators are developed 14, 57. Pdf autophagy and lysosomal dysfunction as emerging. This allowed a rigorous assessment of noncellautonomous effects of autophagy inhibition in the dying cells at drug doses that killed all the drugsensitive cells, but also identifies a potential problem in studies intended to test if autophagy alters cancer cell chemosensitivity. Inhibition of autophagy enhances the anticancer activity of silver nanoparticles jun lin,1 zhihai huang,2 hao wu,2 wei zhou,1 peipei jin,1 pengfei wei,1 yunjiao zhang,1 fang zheng,1 jiqian zhang,1 jing xu,1 yi hu,1 yanhong wang,1 yajuan li,1 ning gu,2, and longping wen1, 1hefei national laboratory for physical sciences at the microscale and school of life sciences. Curcumin and solid lipid curcumin particles induce autophagy. Autophagy is widely studied during analysis of nanoparticle cell interactions for its twoway regulation. Oct 03, 2016 the 2016 nobel prize in physiology or medicine has been awarded to yoshinori ohsumi for his discoveries of mechanisms for autophagy a fundamental process for degrading and recycling cellular. Codelivery nanoparticles of doxorubicin and chloroquine. Accordingly, the role of most of the atg proteins is unknown.
Drug nanorodmediated intracellular delivery of microrna. Involvement of autophagy in tantalum nanoparticleinduced. Autophagy and oxidative stress associated with gold. Macroautophagy autophagy could represent a potential underlying mechanism of this toxicity. However, the poor solubility and limited bioavailability of natural cur limits its application in preventing gbm growth. Changes in cellular endocytosis of silica submicrospheres lead to alteration of autophagy levels.
Here, for the first time, we show a reliable and general mechanism by which nanoparticles induce autophagy and then successfully modulate. A variety of nanoparticles, including rare earth upconversion nanoparticles ucns, have been reported to elicit hepatotoxicity, in most cases through inducing immune response or activating reactive oxygen species. Necrotic, apoptotic and autophagic cell fates triggered by. Intracellular trafficking network and autophagy of phbhhx. However, if autophagy is fundamentally defective in dmdmdx and can be shown to be related to weakness and cardiac dysfunction and if a method for effective delivery of clinically approved doses of rapamycin to muscle tissues that might enhance autophagy and improve endurance can be designed, then a compelling mechanistic link between disturbed.
This was different with a common notion that nanoparticles are. Magnetite iron oxide, fe3o4 nanoparticles have been widely used for drug delivery and magnetic resonance imaging mri. A number of engineered nanoparticles induce autophagy, the main catabolic pathway that regulates. Nov 23, 2015 a number of engineered nanoparticles induce autophagy, the main catabolic pathway that regulates bulk degradation of cytoplasmic material by the lysosomes. We first evaluated the effects of npt on autophagy in evt cells. An indepth understanding of inorganic nmsmodulated autophagy is required for the safety assessment of inorganic nms. Pdf nanoparticlefacilitated autophagy inhibition of. Autophagy may represent a common cellular response to nanomaterials.
Cerium dioxide nanoparticles ceo2 nps have diversified industrial uses, and novel therapeutic applications are actively being pursued. Al 2o 3 nanoparticles 60 nm and 200 nm, nanoamor 2 mgml, anatase tio 2 nanoparticles 25 nm. A read is counted each time someone views a publication summary such as the title, abstract, and list of authors, clicks on a figure, or views or downloads the fulltext. Silica submicrospheres induce autophagy in an endocytosis. Mitophagy induced by nanoparticlepeptide conjugates. Autophagy, as an evolutionarily conserved cellular quality control proc. From the viewpoint of autophagic functions for nanoparticles. Yet for gold nanoparticles aunps, it is not well established whether these particles are biologically toxic. Thus autophagy of nanoparticles plays a key role in deciding their fate after endocytosis. Rare earth oxide nanocrystals as a new class of autophagy.
Targeting autophagy with metalbased nanoparticles as therapy in cancer diseases. Development of nanotechnology calls for a comprehensive understanding of the impact of nanomaterials on biological systems. Pamam nanoparticles promote acute lung injury by inducing. Selenium nanoparticles senps may have a potential role in treating dermal disorders due to its wide therapeutic properties, but there is. Glioma treatment using targeted chemotherapy is still far from satisfactory due to not only the limited accumulation but also the multiple survival mechanisms of glioma cells, including upregulation of both autophagy and programmed cell death ligand 1 pdl1 expression.
Author links open overlay panel xudong zhang a b 1 yichen dong a b 1 xiaowei zeng a b xin liang d xiaoming li. Fine tuning between autophagy and apoptosis induced by nanoparticles or even by other agents is not clearly known but it mainly depends on the types of cell used. Mof nanoparticles with encapsulated autophagy inhibitor in. Apr 24, 2019 the process of autophagy has been conserved over time among all living organisms. Despite the extensive genetic and phenotypic variations present in the different tumors, they frequently share common metabolic alterations, such as autophagy. Autophagy is a selfdegradative process in response to stresses by which damaged macromolecules and organelles are targeted by autophagic vesicles to lysosomes and then eliminated. Previous studies have indicated that reactive oxygen species ros and autophagy are. Induction of oxidative stress, lysosome activation and autophagy by nanoparticles in human brainderived endothelial cells. The interplay between exosomes and autophagy partners in crime. Nanoparticle facilitated autophagy inhibition of cancer stem cells for improved chemotherapeutic effects on glioblastoma article pdf available in journal of materials chemistry b 712. Recent progress in the field of nanotechnology allows for a deeper understanding of their impact on organisms.
In this section, we summarize the most recent studies describing the ability of metallic nanoparticles to overstimulate autophagy and mitophagy in cancer cells selectively. Inhibition of autophagy enhances the anticancer activity. Previously, we have shown the greater apoptotic and anti. Autophagy is a lysosomebased degradative pathway which plays an essential role in maintaining cellular homeostasis. Nanoparticles as a novel class of autophagy activators. Pdf nanoparticles and viruses as mitophagy inducers in.
The autophagic response to polystyrene nanoparticles is mediated. Although autophagy is a dynamic process, the pathway has been delineated into 1. Selenium nanoparticles induce autophagy mediated cell death in. The work offers a unique strategy to combat against autophagy in chemotherapy using nanoparticle drug delivery system. The interactions between nanoparticles and immune cells and their vital function in maintaining tissue homeostasis have become an extremely active research field in nanomedicine 2,3. We found all polystyrene nanoparticles investigated in this study to activate autophagy. Interplay between autophagy and apoptosis mediated by copper. This procedure would disclose an intriguing biological effect induced by nanoparticles, but also enable an alternative mechanism to affect the distribution and fate of nanoparticles inside the cells. It is known that autophagy dysfunctions can promote.
Bec1 nanoparticles display enhanced cytotoxicity to breast cancer cells through induction of autophagy. Structural biology and electron microscopy of the autophagy. Cytotoxicity and autophagy dysfunction induced by different. Gold nanoparticles induce autophagosome accumulation through. Zinc oxide nanoparticles induce autophagy and apoptosis. Review open access autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity stephan t stern, pavan p adiseshaiah and rachael m crist abstract the study of the potential risks associated with the manufacture, use, and disposal of nanoscale materials, and their. Our previous study has found that nano scale silica particles could induce autophagy in primary human umbilical vein endothelial cells huvecs and human hepatocellular carcinoma hepg2 cells. Rapamycin nanoparticles target defective autophagy in. Here we show that aunps, which were taken up by mrc5 human lung fibroblasts in vitro, induce autophagy concomitant with oxidative stress. Autophagy plays vital roles in maintaining delicate balance of promoting.
Nanoparticles nps can be toxic, depending on their physicochemical characteristics. Autophagy and lysosomal dysfunction as emerging mechanisms of. Induction of oxidative stress, lysosome activation and autophagy by nanoparticles in human brainderived endothelial cells article pdf available in biochemical journal 44. Thus it is probable that autophagy in mcf7 cells serves as a survival strategy as inhibition of autophagy results in induction of apoptosis. Our results suggest dispersitydependent autophagic effect as a common cellular response to nanoparticles, reveal the relationship between properties of nanoparticles and autophagy and offer a new. Many of these nanoparticles also induce autophagy, and autophagy inhibition has been shown to decrease ucn. Nanoparticles as a novel class of autophagy activators 280 autophagy 2007. The manipulation of autophagy provides a new opportunity for highly effective anticancer therapies. Al 2 o 3 nanoparticles that are conjugated to either a model tumour antigen or autophagosomes derived from tumour cells resulted in tumour regression. We therefore set up a study aimed to characterize in depth the effects, on autophagy, of macrophage exposure to nps, with a. Iron oxide nanoparticles induce autophagosome accumulation. Zinc oxide nanoparticles harness autophagy to induce cell. We then present the evidence for autophagy related proteins in exosome biogenesis, the emerging roles of. Autophagy is an intracellular mechanism in which cells degrade proteins and organelles by engulfing them in doublemembrane vacuoles known as autophagosomes bergmann, 2007.
The effect of autophagy inhibitors on drug delivery using. Differential autophagic responses to nanosized materials. Autophagy is a new protective mechanism against the cytotoxicity of. Rapamycin nanoparticles target defective autophagy in muscular. There is a lack of mechanistic data concerning the effects of ceo2 nps on primary human cells. Autophagy particles green, mitochondria red, and nuclei blue. Currently, the most widely accepted paradigms of nanomaterial toxicity are oxidative stress and inflammation, but the underlying mechanisms are poorly defined. Images were taken by imagexpress nano system, 40x magnification. Previous studies have shown that nanoparticles from various sources can induce autophagosome accumulation in treated cells. We aimed at characterizing the cytotoxic effects of ceo2 nps in human peripheral blood monocytes.
Depending on the specific physicochemical properties of the nanomaterial, however, nanoparticleinduced autophagy may have different effects on cell physiology, ranging from enhanced autophagic degradation to blockage of autophagic flux. We are currently experiencing intermittent display of pdf links on some. Pdf induction of oxidative stress, lysosome activation and. We also observed formation of autophagosomes together with the uptake of aunps in the lung.
Blanka halamoda kenzaoui, catherine chapuis bernasconi, seher guneyayra, lucienne juilleratjeanneret. Analysis masks shown for autophagy particles and nuclei after using granularity application module in cellreporterxpress software. Iron oxide nanoparticles promote macrophage autophagy and. Zinc oxide particles induce activation of the lysosome. The autophagy substrate p62 was degraded in a dosedependent manner, and autophagy was blocked by autophagy or lysosome inhibitors alone or along with iron oxide nanoparticles, indicating that autophagosome accumulation was mainly due to autophagy induction, rather than blockade of autophagy. Alphaalumina nanoparticles induce efficient autophagy. The novelty of nanoparticles makes their future application promising but it also increases the chance that they will be harmful to organisms that have not evolved to respond to their unique properties. Nanoparticles modulate autophagic effect in a dispersity. To investigate the biosafety of fe3o4 and plgacoated fe3o4. Autophagy is a new protective mechanism against the cytotoxicity of platinum nanoparticles in human trophoblasts skip to main content thank you for visiting.
The present study examined the potential toxic concentrations of zinc oxide nanoparticles. In the present study, it was demonstrated that zinc oxide nanoparticle zonelicited autophagy contributes to tumor cell killing by accelerating the intracellular dissolution of zons and reactive oxygen species ros generation. The interplay between exosomes and autophagy partners in. Although zinc oxide nanoparticles znonps are widely used, they have raised concerns of toxicity in humans. Al 2 o 3 nanoparticles may be a promising adjuvant in the development of therapeutic cancer vaccines. Recently, we showed that the sizedependent cell interaction with quantum dots is autophagy mediated. Recently, we showed that photodynamic therapy pdt with nitrogen. The autophagic response to polystyrene nanoparticles is.
Pdf targeting autophagy using metallic nanoparticles. Taken together, the results show that silver nanoparticles could regulate autophagy via lysosome injury and cell hypoxia in pc. Due to the suitable size for cellular endocytosis, 0. Necrotic, apoptotic and autophagic cell fates triggered by nanoparticles. The autophagic response to polystyrene nanoparticles is mediated by transcription factor eb and depends on surface charge wensi song1, lauren popp1, justin yang 1, ayushi kumar1, varun shenoy gangoli1 and laura segatori1,2,3 abstract background. Of particular interest is the autophagic response to zinc oxide particles, as autophagy is the. Jul 18, 2016 autophagy is a cellular pathway involved in degradation of damaged organelles and proteins in order to keep cellular homeostasis. Autophagy is a new protective mechanism against the. Pdf on sep 19, 2017, housam eidi and others published nanoparticles and viruses as mitophagy inducers in immune cells find, read and cite all the research you need on researchgate. However, in the above study, autophagy inhibitor is a free drug, and it has not been loaded in nps with an anticancer drug, which may lead side effects of autophagy inhibitor or unknown adverse reactions to normal tissues of the body.
Silica nanoparticles induce autophagy and endothelial. However, the underlying mechanism is still not clear. Exosomes are cargoladen extracellular vesicles that arise from endosomederived. Ceo2 nps and their suspensions were thoroughly characterized. Autophagy is a highly regulated bulk degradation process that plays a key role in the maintenance of cellular homeostasis. Carbon nanotubes, but not spherical nanoparticles, block. Zinc oxide nanoparticles induce apoptosis and autophagy in human ovarian cancer cells article pdf available in international journal of nanomedicine volume 12. Pdf autophagy represents a cells response to stress. Bioactive silica nanoparticles promote osteoblast differentiation through stimulation of autophagy and direct association with lc3 and p62 shinwoo ha, emory university m. Two methods, manual counting or the cell proliferation reagent wst1 roche. Autophagy and the pi3kaktmtor signaling pathway play significant roles in glioblastoma multiforme gbm cell death and survival. Involvement of autophagy in tantalum nanoparticleinduced osteoblast proliferation chengrong kang,1,2 limin wei,1 bin song,1 liangjiao chen,3 jia liu,1 bin deng,4 xuan pan,2 longquan shao1 1department of stomatology, nanfang hospital, southern medical university, 2department of stomatology, the first affiliated hospital of guangdong pharmaceutical university, 3department of orthodontics, key. Neale weitzmann, emory university george beck jr, emory university journal title.
Pdf induction of oxidative stress, lysosome activation. Alphaalumina nanoparticles induce efficient autophagy dependent crosspresentation and potent antitumour response haiyan li, yuhuan li, jun jiao, hongming hu supplementary methods. Silica nanoparticles enhance autophagic activity, disturb endothelial. Carbon nanotubes, but not spherical nanoparticles, block autophagy by a shaperelated targeting of lysosomes in murine macrophages vanessa cohignac a,b, marion julie landry, audrey ridoux a, mathieu pinault c, balasubramanyam annangi a,b. Nanosized al 2 o 3 particleinduced autophagy reduces. As a novel carrier, zif8 nanoparticles were used in this work to control the release of an autophagy inhibitor, 3methyladenine 3ma, and prevent it from dissipating in a.
Depending on the specific physicochemical properties of the nanomaterial, however, nanoparticle induced autophagy may have different effects on cell physiology, ranging from enhanced autophagic degradation to blockage of autophagic. Autophagy plays a vital role in cytoplasmic renewal, elimination of intercellular aggregateprone proteins and clearance of pathogens 9. Previous studies have indicated that reactive oxygen species ros and autophagy. Induction of oxidative stress, lysosome activation and. It is becoming increasingly clear that stiff, nonbiodegradable nanoparticles cause the generation of reactive oxygen species ros and the initiation of autophagy,,, yet the underlying. For example, phsensitive polymeric nano particles induce autophagy at low concentration, while a high dose blocks autophagic flux. Noncellautonomous effects of autophagy inhibition in tumor. This study will provide an experimental basis for the cancer therapy of nanomaterials. Autophagy consists of several sequential stepssequestration, transport to lysosomes, degradation, and utilization of degradation productsand each step may exert different function. Iron oxide nanoparticles and induced autophagy in human. Markers of autophagy have been detected upon cellular uptake of a variety of engineered nanoparticles, includ ing metal oxide nanoparticles 23, 24, quantum. Titanium dioxide nanoparticles nano tio2 are known to induce autophagy in cells, but little has been reported about the mechanism of this process in podocytes and the role of autophagy in podocyte death. Pdf despite the extensive genetic and phenotypic variations present in the different tumors, they frequently share common metabolic.
Autophagy or autophagocytosis from the ancient greek autophagos, meaning selfdevouring1 and kytos, meaning hollow2 is the natural, regulated, destructive mechanism of the cell that disassembles unnecessary or dysfunctional components. The effect of autophagy inhibitors on drug delivery using biodegradable polymer nanoparticles in cancer treatment. Silica nanoparticles induce autophagy and endothelial dysfunction via the pi3kaktmtor signaling pathway junchao duan,1,2 yongbo yu,1,2 yang yu,1,2 yang li,1,2 ji wang,1,2 weijia geng,1,2 lizhen jiang,1,2 qiuling li,1,2 xianqing zhou,1,2 zhiwei sun1,2 1school of public health, capital medical university, beijing, 2beijing key laboratory of environmental toxicology, capital medical university. The function of autophagy is still not clearly understood but it is generally thought to be a natural process to maintain cellular homeostasis as well as a cellular response to starvation, infection or. The potential role of other endo and exogenous nanoparticles in terms of autophagy is discussed here. Toxic pamam nanoparticles induce autophagic cell death in a549 cells. Although autophagy is a key metabolic pathway for maintaining the metabolic homeostasis of cells, no study has determined whether autophagy induced by al2o3 particles is involved in the. Nanoparticles modulate autophagic effect in a dispersitydependent. A number of engineered nanoparticles induce autophagy, the main catabolic pathway that regulates bulk degradation of cytoplasmic material by the lysosomes. Nanotio 2 induces autophagy to protect against cell death. Herein, we proposed a combined therapeutic regimen based on functional gold nanoparticles aunpsenabled chemotherapy. Till now, nondegradable nanoparticles, such as gold, silica and tio 2 nanoparticles, have been reported to induce oxidative damage and autophagy 10, 11. Nov 27, 2018 despite the extensive genetic and phenotypic variations present in the different tumors, they frequently share common metabolic alterations, such as autophagy.
Similar to other nanoparticles, nps also induced intracellular autophagy and were then degraded via endolysosomal pathways. Silver nanoparticles regulate autophagy through lysosome. Klionsky j apharmaceutics research center, institute of neuropharmacology, kerman university of medical. The process is similar in single cellular organisms like yeast to multicellular organisms like humans. Molecular links among nonbiodegradable nanoparticles. The fact is supported by europium hydroxide euiiioh 3 nanorods, which induce autophagy and enhance the autophagymedi. Autophagy and oxidative stress associated with gold nanoparticles. Two components of this system, exosome biogenesis and autophagy, are linked by the endolysosomal pathway. Gold nanoparticles induce autophagosome accumulation. Previous studies have shown that many metalbased nanoparticles including fe3o4 nanoparticles can induce autophagosome accumulation in treated cells. Nanotechnology encompasses topics ranging from nanodevices, nanosensors and nanorobots to nanomedicines. Curcumin cur has been reported to prevent several cancers, including gbm. Alphaalumina nanoparticles induce efficient autophagy dependent crosspresentation and potent antitumour.
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