Mitophagy–lysosomal pathway is involved in silver nanoparticle-induced apoptosis in A549 cells

Li, Jiangyan; Chang, Xiaoru; Shang, Mengting; Niu, Shuyan; Zhang, Wenli; Zhang, Bangyong; Huang, Wenyan; Wu, Tianshu; Zhang, Ting; Tang, Meng; Yang, Xue

doi:10.1016/j.ecoenv.2020.111463

Cited by 34 publications

(21 citation statements)

References 42 publications

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“…AgNP-related ROS give rise to oxidatively modified proteins, which become labeled for degradation and eventually activate autophagic flux via redox signaling [114,115]. Additionally, AgNPs may lead to mitotoxicity-triggered mitophagy which is a form of selective autophagy [114,116,117]. In a recent study, AgNPs were shown to induce HiF-1α activation, thereby ultimately activating autophagy through the AMPK-mTOR pathway in PC-3 prostate cancer cells [89].…”

Section: Intracellular Pathways Triggered By Agnpsmentioning

confidence: 99%

Cancer Therapy by Silver Nanoparticles: Fiction or Reality?

Kovács

Igaz

Gopisetty

et al. 2022

IJMS

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As an emerging new class, metal nanoparticles and especially silver nanoparticles hold great potential in the field of cancer biology. Due to cancer-specific targeting, the consequently attenuated side-effects and the massive anti-cancer features render nanoparticle therapeutics desirable platforms for clinically relevant drug development. In this review, we highlight those characteristics of silver nanoparticle-based therapeutic concepts that are unique, exploitable, and achievable, as well as those that represent the critical hurdle in their advancement to clinical utilization. The collection of findings presented here will describe the features that distinguish silver nanoparticles from other anti-cancer agents and display the realistic opportunities and implications in oncotherapeutic innovations to find out whether cancer therapy by silver nanoparticles is fiction or reality.

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Section: Intracellular Pathways Triggered By Agnpsmentioning

confidence: 99%

Cancer Therapy by Silver Nanoparticles: Fiction or Reality?

Kovács

Igaz

Gopisetty

et al. 2022

IJMS

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“…However, light microscopy cannot detect dissolved Ag, and significant evidence suggests that AgNPs are trafficked to lysosomes, where they may dissolve and could potentially result in Ag ions being released and moving to mitochondria, , a possibility that would fit with the “Trojan horse mechanism” . Therefore, to investigate potential AgNP-mitochondrial colocalization by a different and more quantitative approach, we measured the total Ag content in subcellular fractions using ICP-MS. After exposure to LC 30 concentrations of AgNPs and AgNO 3 for 24 h, mitochondria were isolated from cells.…”

Section: Resultsmentioning

confidence: 99%

“…Silver nanoparticles (AgNPs) have been a rapidly increasing product category in the nanotechnology industry, resulting in potential risk in human and environmental health. − Despite numerous publications on the toxicity of various types of AgNPs in vitro and in vivo , − details of AgNP toxicity remain unclear. Extensive research indicates that the toxicity of AgNPs and the underlying molecular mechanisms depend on the model system and nanoparticle properties.…”

Section: Introductionmentioning

confidence: 99%

Lack of Detectable Direct Effects of Silver and Silver Nanoparticles on Mitochondria in Mouse Hepatocytes

Wang

Mello

Zucker

et al. 2021

Environ. Sci. Technol.

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Silver nanoparticles (AgNPs) are well-proven antimicrobial nanomaterials, yet little is elucidated regarding the mechanism underlying cytotoxicity induced by these nanoparticles. Here, we tested the hypothesis that mitochondria are primary intracellular targets of two AgNPs and silver ions in mouse hepatocytes (AML12) cultured in glucose- and galactose-based media. AML12 cells were more sensitive to mitochondrial uncoupling when grown with galactose rather than glucose. However, 24 h treatments with 15 nm AgNPs and 6 nm GA-AgNPs (5 and 10 μg/mL) and AgNO3 (1 and 3 μg/mL), concentrations that resulted in either 10 or 30% cytotoxicity, failed to cause more toxicity to AML12 cells grown on galactose than glucose. Furthermore, colocalization analysis and subcellular Ag quantification did not show any enrichment of silver content in mitochondria in either medium. Finally, the effects of the same exposures on mitochondrial respiration were mild or undetectable, a result inconsistent with mitochondrial toxicity causing cell death. Our results suggest that neither ionic Ag nor the AgNPs that we tested specifically target mitochondria and are inconsistent with mitochondrial dysfunction being the primary cause of cell death after Ag exposure under these conditions.

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“…The next stress marker evaluated was HSP70, which is known to be activated following AgNP exposure [ 41 ]. In the absence of AgNPs, all in vitro models displayed equivalent HSP70 levels ( Figure 5 B).…”

Section: Resultsmentioning

confidence: 99%

Implementation of a Dynamic Co-Culture Model Abated Silver Nanoparticle Interactions and Nanotoxicological Outcomes In Vitro

et al. 2021

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The incorporation of engineered nanoparticles (NPs) into everyday consumer goods, products, and applications has given rise to the field of nanotoxicology, which evaluates the safety of NPs within biological environments. The unique physicochemical properties of NPs have made this an insurmountable challenge, as their reactivity and variable behavior have given rise to discrepancies between standard cell-based in vitro and animal in vivo models. In this study, enhanced in vitro models were generated that retained the advantages of traditional cell cultures, but incorporated the modifications of (1) inclusion of an activated immune element and (2) the presence of physiologically-relevant dynamic flow. Following verification that the human alveolar epithelial and macrophage (A549/U937) co-culture could be successfully sustained under both static and dynamic conditions, these cultures, in addition to a standard A549 static model, were challenged with 10 nm citrate coated silver NPs (AgNPs). This work identified a reshaping of the AgNP-cellular interface and differential biological responses following exposure. The presence of dynamic flow modified cellular morphology and reduced AgNP deposition by approximately 20% over the static exposure environments. Cellular toxicity and stress endpoints, including reactive oxygen species, heat shock protein 70, and secretion of pro-inflammatory cytokines, were found to vary as a function of both cellular composition and flow conditions; with activated macrophages and fluid flow both mitigating the severity of AgNP-dependent bioeffects. This work highlights the possibility of enhanced in vitro systems to assess the safety of engineered NPs and demonstrates their effectiveness in elucidating novel NP-cellular interactions and toxicological profiles.

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Mitophagy–lysosomal pathway is involved in silver nanoparticle-induced apoptosis in A549 cells

Cited by 34 publications

References 42 publications

Cancer Therapy by Silver Nanoparticles: Fiction or Reality?

Cancer Therapy by Silver Nanoparticles: Fiction or Reality?

Lack of Detectable Direct Effects of Silver and Silver Nanoparticles on Mitochondria in Mouse Hepatocytes

Implementation of a Dynamic Co-Culture Model Abated Silver Nanoparticle Interactions and Nanotoxicological Outcomes In Vitro

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