C60(Nd) nanoparticles enhance chemotherapeutic susceptibility of cancer cells by modulation of autophagy

Wei, Pengfei; Zhang, Li; Lu, Yang; Man, Na; Wen, Longping

doi:10.1088/0957-4484/21/49/495101

Cited by 92 publications

(61 citation statements)

References 34 publications

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“…723 It is worth noting that lysosomal proteases fall into three general groups, cysteine, aspartic acid and serine proteases. Therefore, the fact that leupeptin, a serine and cysteine protease inhibitor, has little or no effect does not necessarily indicate that lysosomal degradation is not taking place; a combination of leupeptin, pepstatin A and E-64d may be a more effective treatment.…”

Section: 696mentioning

confidence: 99%

Guidelines for the use and interpretation of assays for monitoring autophagy

Klionsky¹,

Abdalla²,

Abeliovich³

et al. 2012

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In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

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Section: 696mentioning

confidence: 99%

Guidelines for the use and interpretation of assays for monitoring autophagy

Klionsky¹,

Abdalla²,

Abeliovich³

et al. 2012

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“…With unique physicochemical properties, nanomaterials are emerging as a new class of autophagy inducers in recent years. 4 A variety of engineered nanomaterials, such as quantum dots, 5 fullerene C60 and its derivatives, 6,7 gold and iron core-gold shell nanoparticle, 8,9 graphene, 10 iron oxide, 11 MnO nanocrystals, 12 rare earth nanocrystals, [13][14][15][16] VO 2 nanocrystals, 17 Ni-Co alloy nanocrystal, 18 europium hydroxide nanorods 19 etc., elicit an autophagic response in the various cancer cell culture systems examined. An elevated level of autophagy during tumor development and in cancer therapy has paradoxically been reported to have roles in promoting both cell survival and cell death.…”

Section: Introductionmentioning

confidence: 99%

“…In most of the circumstances, elevated autophagy after nanomaterial treatment leads to increased cell death. 6,7,9,12,15,18 But in rare situations, nanomaterial-induced autophagy may also promote cell survival. 17 Silver nanoparticles (Ag NPs) exhibit a variety of biological effects, such as antibacterial, 24,25 antifungal, 26,27 antiviral, [28][29][30] and antiinflammatory, 31,32 and thus are attracting interest for a wide range of biomedical applications.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of autophagy enhances the anticancer activity of silver nanoparticles

et al. 2014

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Abbreviations: ANXA5, annexin A5; CASP3, caspase 3, apoptosis-related cysteine peptidase; CTSB, cathepsin B; DLS, dynamic light scattering; DMEM, Dulbecco's Modified Eagle's medium; EGFP-LC3, enhanced green fluorescent protein-tagged LC3; ICP-MS, inductively coupled plasma-mass spectrometry; I-MEF, immortalized mouse embryonic fibroblast; MDC, monodansylcadaverine; MTOR, mechanistic target of rapamycin; P-MEF, primary mouse embryonic fibroblast; PI, propidium iodide; PI3K, phosphoinositide 3-kinase; PtdIns3K, phosphatidylinositol 3-kinase; PVP, polyvinylpyrrolidone; RPS6KB, ribosomal protein S6 kinase, 70 kDa; s.c., subcutaneously; SQSTM1, sequestosome 1; TEM, transmission electron microscopy; TUNEL, terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTPdigoxigenin nick end labeling; UV-Vis, ultraviolet visible; XRD, X-ray diffraction.Silver nanoparticles (Ag NPs) are cytotoxic to cancer cells and possess excellent potential as an antitumor agent. A variety of nanoparticles have been shown to induce autophagy, a critical cellular degradation process, and the elevated autophagy in most of these situations promotes cell death. Whether Ag NPs can induce autophagy and how it might affect the anticancer activity of Ag NPs has not been reported. Here we show that Ag NPs induced autophagy in cancer cells by activating the PtdIns3K signaling pathway. The autophagy induced by Ag NPs was characterized by enhanced autophagosome formation, normal cargo degradation, and no disruption of lysosomal function. Consistent with these properties, the autophagy induced by Ag NPs promoted cell survival, as inhibition of autophagy by either chemical inhibitors or ATG5 siRNA enhanced Ag NPs-elicited cancer cell killing. We further demonstrated that wortmannin, a widely used inhibitor of autophagy, significantly enhanced the antitumor effect of Ag NPs in the B16 mouse melanoma cell model. Our results revealed a novel biological activity of Ag NPs in inducing cytoprotective autophagy, and inhibition of autophagy may be a useful strategy for improving the efficacy of Ag NPs in anticancer therapy.

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“…The chemo-sensitization effect of nano-C 60 was autophagy-mediated and required functional Atg5, a key player in the autophagic signaling pathway. Compared to nC 60 , nC 60 (Nd) is more effective to induce autophagy and to sensitize chemotherapy [39]. These studies imply a novel application of nC 60 /C 60 (Nd) nanoparticle in cancer therapy.…”

Section: And C 60 Derivativesmentioning

confidence: 91%

Autophagy as new emerging cellular effect of nanomaterials

et al. 2013

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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. ...

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C60(Nd) nanoparticles enhance chemotherapeutic susceptibility of cancer cells by modulation of autophagy

Cited by 92 publications

References 34 publications

Guidelines for the use and interpretation of assays for monitoring autophagy

Guidelines for the use and interpretation of assays for monitoring autophagy

Inhibition of autophagy enhances the anticancer activity of silver nanoparticles

Autophagy as new emerging cellular effect of nanomaterials

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