Silver nanoparticles of different sizes induce a mixed type of programmed cell death in human pancreatic ductal adenocarcinoma

Zielińska, Ewelina; Zauszkiewicz-Pawlak, Agata; Wójcik, Michał; Inkielewicz‐Stępniak, Iwona

doi:10.18632/oncotarget.22563

Cited by 111 publications

(109 citation statements)

References 91 publications

(117 reference statements)

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“…While it has also been reported that chronic low-dose AgNPs exposure resulted in to HaCaT noncancerous cell transformation, and despite the activation of EGF receptors and the related gene expression that enhances cell proliferation, cells treated with a high dose of AgNPs within a short time showed inhibited proliferation [121]. Ag-NPs have been observed to have a higher cytotoxic effect on PANC1 pancreatic cancer cells than on non-tumor cells of the same tissue [122]. Furthermore, combining AgNPs with drugs synergistically enhanced the cytotoxicity to cancer cells [116].…”

Section: Silver Nanoparticles-induced Toxicity and The Possible Role mentioning

confidence: 99%

The Current Understanding of Autophagy in Nanomaterial Toxicity and Its Implementation in Safety Assessment-Related Alternative Testing Strategies

Chen

Liao

et al. 2020

IJMS

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Nanotechnology has rapidly promoted the development of a new generation of industrial and commercial products; however, it has also raised some concerns about human health and safety. To evaluate the toxicity of the great diversity of nanomaterials (NMs) in the traditional manner, a tremendous number of safety assessments and a very large number of animals would be required. For this reason, it is necessary to consider the use of alternative testing strategies or methods that reduce, refine, or replace (3Rs) the use of animals for assessing the toxicity of NMs. Autophagy is considered an early indicator of NM interactions with cells and has been recently recognized as an important form of cell death in nanoparticle-induced toxicity. Impairment of autophagy is related to the accelerated pathogenesis of diseases. By using mechanism-based high-throughput screening in vitro, we can predict the NMs that may lead to the generation of disease outcomes in vivo. Thus, a tiered testing strategy is suggested that includes a set of standardized assays in relevant human cell lines followed by critical validation studies carried out in animals or whole organism models such as C. elegans (Caenorhabditis elegans), zebrafish (Danio rerio), and Drosophila (Drosophila melanogaster)for improved screening of NM safety. A thorough understanding of the mechanisms by which NMs perturb biological systems, including autophagy induction, is critical for a more comprehensive elucidation of nanotoxicity. A more profound understanding of toxicity mechanisms will also facilitate the development of prevention and intervention policies against adverse outcomes induced by NMs. The development of a tiered testing strategy for NM hazard assessment not only promotes a more widespread adoption of non-rodent or 3R principles but also makes nanotoxicology testing more ethical, relevant, and cost- and time-efficient.

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Section: Silver Nanoparticles-induced Toxicity and The Possible Role mentioning

confidence: 99%

The Current Understanding of Autophagy in Nanomaterial Toxicity and Its Implementation in Safety Assessment-Related Alternative Testing Strategies

Chen

Liao

et al. 2020

IJMS

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“…[9][10][11][12][13] Among metallic nanoparticles, silver nanoparticles (AgNPs) have high biomedical relevance primarily due to their antimicrobial properties. [14][15][16] AgNPs are also reported to be cytotoxic to cancers including those of the breast, 17 ovary, 18 brain, [19][20][21] cervix, 22 liver, 23 colon, 24 lung, 25 pancreas, 26 and blood. [27][28][29][30] We recently observed that exposure to AgNPs in vitro was lethal to three TNBC cell lines at doses that were not cytotoxic to non-cancerous breast cells or immortalized cells derived from kidney, liver, or monocyte/macrophages.…”

Section: Introductionmentioning

confidence: 99%

Silver nanoparticles selectively treat triple‐negative breast cancer cells without affecting non‐malignant breast epithelial cells in vitro and in vivo

et al. 2019

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Silver nanoparticles (AgNPs) show promise for treatment of aggressive cancers including triple‐negative breast cancer (TNBC) in preclinical cancer models. For clinical development of AgNP‐based therapeutics, it will be necessary to clearly define the specific physicochemical features of the nanoparticles that will be used, and to tie these properties to biological outcomes. To fill this knowledge gap, we performed thorough structure/function, mechanistic, safety, and efficacy studies to assess the potential for AgNPs to treat TNBC. We establish that AgNPs, regardless of size, shape, or stabilizing agent, are highly cytotoxic to TNBC cells at doses that are not cytotoxic to non‐malignant breast epithelial cells. In contrast, TNBC cells and non‐malignant breast epithelial cells are similarly sensitive to exposure to silver cation (Ag+), indicating that the nanoparticle formulation is essential for the TNBC‐specific cytotoxicity. Mechanistically, AgNPs are internalized by both TNBC and non‐malignant breast cells, but are rapidly degraded only in TNBC cells. Exposure to AgNPs depletes cellular antioxidants and causes endoplasmic reticulum stress in TNBC cells without causing similar damage in non‐malignant breast epithelial cells. AgNPs also cause extensive DNA damage in 3D TNBC tumor nodules in vitro, but do not disrupt the normal architecture of breast acini in 3D cell culture, nor cause DNA damage or induce apoptosis in these structures. Lastly, we show that systemically administered AgNPs are effective at non‐toxic doses for reducing the growth of TNBC tumor xenografts in mice. This work provides a rationale for development of AgNPs as a safe and specific TNBC treatment.

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“…Nanosilver is mainly seen to be taken up into cells through endocytosis into vesicles, although diffusion of the nanosilver across the cell membrane into the cytoplasm may also occur [51,[54][55][56][57]. It has been suggested that nanosilver may be able to diffuse across the membrane through induced lipid peroxidation and disruption of the plasma membrane [21,58].…”

Section: Uptake Of Nanosilvermentioning

confidence: 99%

“…AgNO3 is most commonly used as an Ag + ion control [47]; however, silver acetate (C2H3AgO2) [48,49] or silver carbonate (Ag2CO3) have also been used [50]. If the Ag + ion control is used at the same concentration as the nanosilver treatment dose, the AgNO3 will be much more toxic since there are many more silver ions present than in the nanosilver solution [18,51]. In order to treat cells with a relevant concentration of Ag + ions for the Ag + ion control: (1) ICP-MS may be performed on the nanosilver solution to determine the concentration of Ag + ions that are released [11,15,16,51], (2) viability assays may be done to determine the treatment concentrations for both the Ag + ion control and nanosilver that gives the same % cell viability [52], or (3) the nanosilver particles can be incubated in media for an experimentally relevant time, removed by centrifugation, and the cells then treated with the remaining media containing any released Ag + ions [40,53].…”

Section: Introductionmentioning

confidence: 99%

A Current Overview of the Molecular Effects of Nanosilver

Cameron¹,

Willmore²

2018

Preprint

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Nanosilver plays an important role in nanoscience and nanotechnology, and is becoming increasingly used for applications in nanomedicine. Nanosilver ranges in size from one to one hundred nanometers. Smaller particles more readily enter cells and interact with the cellular components. The exposure dose, particle size, coating, and aggregation state of the nanosilver, as well as the cell type or organism that it is tested on, all have a large determining factor on the effect and potential toxicity of nanosilver. A high exposure dose to nanosilver alters the cellular stress responses and initiates cascades of signaling that can eventually trigger organelle autophagy and apoptosis. This review summarizes the current knowledge of the effects of nanosilver on cellular metabolic function and response to stress. Both the causative effects of nanosilver on oxidative stress, endoplasmic reticulum stress, and hypoxic stress, as well as the effects of nanosilver on the responses to such stresses, are outlined. The interactions and effects of nanosilver on cellular uptake, oxidative stress (reactive oxygen species), inflammation, hypoxic response, mitochondrial function, endoplasmic reticulum function and the unfolded protein response, autophagy and apoptosis, angiogenesis, epigenetics, genotoxicity, and cancer development and tumorigenesis, as well as other pathway alterations are examined in this review.

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Silver nanoparticles of different sizes induce a mixed type of programmed cell death in human pancreatic ductal adenocarcinoma

Cited by 111 publications

References 91 publications

The Current Understanding of Autophagy in Nanomaterial Toxicity and Its Implementation in Safety Assessment-Related Alternative Testing Strategies

The Current Understanding of Autophagy in Nanomaterial Toxicity and Its Implementation in Safety Assessment-Related Alternative Testing Strategies

Silver nanoparticles selectively treat triple‐negative breast cancer cells without affecting non‐malignant breast epithelial cells in vitro and in vivo

A Current Overview of the Molecular Effects of Nanosilver

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