Anti-proliferative activity of silver nanoparticles

By P. Asharani, M. Hande, S. Valiyaveettil. BMC Cell Biology, 2009

645 citations recorded by the source corpus.

BackgroundNanoparticles possess exceptional physical and chemical properties which led to rapid commercialisation. Silver nanoparticles (Ag-np) are among the most commercialised nanoparticles due to their antimicrobial potential. Ag-np based cosmetics, therapeutic agents and household products are in wide use, which raised a public concern regarding their safety associated with human and environmental use. No safety regulations are in practice for the use of these nanomaterials. The interactions of nanomaterials with cells, uptake mechanisms, distribution, excretion, toxicological endpoints and mechanism of action remain unanswered.ResultsNormal human lung fibroblasts (IMR-90) and human glioblastoma cells (U251) were exposed to different doses of Ag-nps in vitro. Uptake of Ag-nps occurred mainly through endocytosis (clathrin mediated process and macropinocytosis), accompanied by a time dependent increase in exocytosis rate. The electron micrographs revealed a uniform intracellular distribution of Ag-np both in cytoplasm and nucleus. Ag-np treated cells exhibited chromosome instability and mitotic arrest in human cells. There was efficient recovery from arrest in normal human fibroblasts whereas the cancer cells ceased to proliferate. Toxicity of Ag-np is mediated through intracellular calcium (Ca2+) transients along with significant alterations in cell morphology and spreading and surface ruffling. Down regulation of major actin binding protein, filamin was observed after Ag-np exposure. Ag-np induced stress resulted in the up regulation of metallothionein and heme oxygenase -1 genes.ConclusionHere, we demonstrate that uptake of Ag-np occurs mainly through clathrin mediated endocytosis and macropinocytosis. Our results suggest that cancer cells are susceptible to damage with lack of recovery from Ag-np-induced stress. Ag-np is found to be acting through intracellular calcium transients and chromosomal aberrations, either directly or through activation of catabolic enzymes. The signalling cascades are believed to play key roles in cytoskeleton deformations and ultimately to inhibit cell proliferation.

Subfields: Biomaterials, Materials Chemistry, Oncology

View Paper: https://www.semanticscholar.org/paper/e2042dc9645d8af9a3a6749ec3f08474ab2ec13b

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In Biomaterials

1. Kenneth A. Dawson
2. Iseult Lynch
3. Bengt Fadeel
4. C. Liao
5. S. Tjong
6. Yuchao Li
7. Eleonore Fröhlich
8. C. Murphy

In Materials Chemistry

1. Kenneth A. Dawson
2. R. Prasad
3. Iseult Lynch
4. Sang Hun Lee
5. B. Reidy
6. Bong-Hyun Jun
7. Anu Kumar
8. Vinod Yadav

In Oncology

1. C. Liao
2. S. Tjong
3. Yuchao Li

Citations in the corpus

• Silver Nanoparticles: Synthesis and Application for Nanomedicine (2019, background): “Apart from these cellular mechanisms, AgNPs have also shown anti-angiogenic and anti-proliferative properties [123,124].”
• Mechanisms of Silver Nanoparticle Release, Transformation and Toxicity: A Critical Review of Current Knowledge and Recommendations for Future Studies and Applications (2013, methodology): “However, due to sample preparation, nanoparticles cannot be observed in suspension, so if TEM is the only method used [83] the behaviour of the particles in suspension remains largely unknown.”
• Molecular Toxicity Mechanism of Nanosilver (2014, neutral): “[71] AshaRani P, Hande MP, Valiyaveettil S.”
• Bactericidal and Cytotoxic Properties of Silver Nanoparticles (2019, methodology): “Figure 17a,b summarize possible mechanisms of AgNPs-, or Ag+-induced toxicity in mammalian cells [190,192].”
• Biogenic synthesis of silver nanoparticles using Nicotiana tobaccum leaf extract and study of their antibacterial effect (2011, background): “An anti-proliferative activity of silver nanoparticles against human cancer cells have been reported (Rani et al., 2009).”
• Mechanistic Basis of Antimicrobial Actions of Silver Nanoparticles (2016, background): “In contrast, Asharani et al. (2009a) showed the direct role of AgNPs in the dysfunctioning of mitochondrial and apoptotic death in lung fibroblast IMR-90 cells.”
• Silver nanoparticles: Synthesis, medical applications and biosafety (2020, background): “AgNPs-treated cancer cells may exhibit DNA methylation, DNA base pairing errors, DNA repair defects and increased chromosomal aberrations [209, 248, 258].”
• Size-dependent cytotoxicity of silver nanoparticles in human lung cells: the role of cellular uptake, agglomeration and Ag release (2014, background): “Induction of autophagy has been reported for several engineered nanoparticles, including AgNPs and Ag nanowires [37,39], and may represent a common cellular response to nanoparticles.”