Molecular and Cellular Risk Assessment of Healthy Human Cells and Cancer Human Cells Exposed to Nanoparticles

Helal-Neto, Edward; Silva, Aline Oliveira da; Saldanha-Gama, Roberta; Brandão-Costa, Renata Machado; Alencar, Luciana Magalhães Rebêlo; Santos, Clenilton Costa dos; Martínez‐Máñez, Ramón; Ricci-Júnior, Eduardo; Alexis, Frank; Morandi, Verônica; Barja‐Fidalgo, Christina; Santos-Oliveira, Ralph

doi:10.3390/ijms21010230

Cited by 16 publications

(11 citation statements)

References 74 publications

(81 reference statements)

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“…Human cell lines from melanoma (MV3), breast cancer (MDA-MB-231) and prostate cancer (PC-3) were obtained from Cell Bank of Rio de Janeiro (Rio de Janeiro, Brazil). These cells were routinely maintained (separately) in DMEM (MV3, MDA-MB-231 and HEK293T) or in RPMI medium (PC-3) supplemented with 10% FBS, NaHCO3 (3.7 g/l), HEPES (5.2 g/l), penicillin (0.5 U/ml) and streptomycin (0.5 mg/ml) [30].…”

Section: Human Cells Culturesmentioning

confidence: 99%

Radioactive gold nanocluster (198-AuNCs) showed inhibitory effects on cancer cells lines

Xuan

Silva

Nunes

et al. 2020

Artificial Cells, Nanomedicine, and Biotechnology

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Cancer is a global epidemic disease responsible for over ten millions death worldwide. The early diagnosis and the precise treatment with reduced adverse reactions are the main goal worldwide. In this study, we produced, characterized and evaluated (in vitro) in three different cancer cell lines (protaste, breast and melanoma) a radioactive gold nanocluster (R-AuNC) (198 Au25(Capt)18). The pharmacokinetics as the influence in the ABC transporter (MRP1 Efflux Transporter Protein) was also evaluated. The results showed that R-AuNC (198 Au25(Capt)18) are capable to kill the cancer cells lines of protaste, breast and melanoma. The pharmacokinetics showed a fast clearance and great volume of distribution, confirming the use of R-AuNC as nanomedicine for cancer treatment. Finally, the ABC transporter assay corroborated that the R-AuNC (198 Au25(Capt)18) has no risk of being pumped out of cells by this efflux transporter. The results validate the use of gold nanoparticles as therapeutic nanomedicine for cancer treatment.

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Section: Human Cells Culturesmentioning

confidence: 99%

Radioactive gold nanocluster (198-AuNCs) showed inhibitory effects on cancer cells lines

Xuan

Silva

Nunes

et al. 2020

Artificial Cells, Nanomedicine, and Biotechnology

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“…Broad applications of magnetic nanoparticles (MNPs)—and those coated with biocompatible silica and polymers—include contrast agents for magnetic resonance imaging, in vivo tracers, transfection agents, and drug delivery tools [ 1 – 5 ]. Nanoparticles (NPs) have also enabled various technological advances in biotechnology, materials science, engineering, and biomedicine [ 6 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Nanomaterial-induced toxicity (nanotoxicity) is mostly mediated by redox imbalance, including reactive oxygen species (ROS) production, mitochondrial dysfunction, and energy metabolism dysfunction [ 13 – 20 ]. However, detailed biological evaluations for the mechanisms of the redox imbalance are still limited [ 5 , 21 ]. Therefore, an increasing number of studies are focusing on reducing nanotoxicity and identifying the relevant mechanisms [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Silica-coated magnetic-nanoparticle-induced cytotoxicity is reduced in microglia by glutathione and citrate identified using integrated omics

et al. 2021

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Background Nanoparticles have been utilized in brain research and therapeutics, including imaging, diagnosis, and drug delivery, owing to their versatile properties compared to bulk materials. However, exposure to nanoparticles leads to their accumulation in the brain, but drug development to counteract this nanotoxicity remains challenging. To date, concerns have risen about the potential toxicity to the brain associated with nanoparticles exposure via penetration of the brain blood barrier to address this issue. Methods Here the effect of silica-coated-magnetic nanoparticles containing the rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)] were assessed on microglia through toxicological investigation, including biological analysis and integration of transcriptomics, proteomics, and metabolomics. MNPs@SiO2(RITC)-induced biological changes, such as morphology, generation of reactive oxygen species, intracellular accumulation of MNPs@SiO2(RITC) using transmission electron microscopy, and glucose uptake efficiency, were analyzed in BV2 murine microglial cells. Each omics data was collected via RNA-sequencing-based transcriptome analysis, liquid chromatography-tandem mass spectrometry-based proteome analysis, and gas chromatography- tandem mass spectrometry-based metabolome analysis. The three omics datasets were integrated and generated as a single network using a machine learning algorithm. Nineteen compounds were screened and predicted their effects on nanotoxicity within the triple-omics network. Results Intracellular reactive oxygen species production, an inflammatory response, and morphological activation of cells were greater, but glucose uptake was lower in MNPs@SiO2(RITC)-treated BV2 microglia and primary rat microglia in a dose-dependent manner. Expression of 121 genes (from 41,214 identified genes), and levels of 45 proteins (from 5918 identified proteins) and 17 metabolites (from 47 identified metabolites) related to the above phenomena changed in MNPs@SiO2(RITC)-treated microglia. A combination of glutathione and citrate attenuated nanotoxicity induced by MNPs@SiO2(RITC) and ten other nanoparticles in vitro and in the murine brain, protecting mostly the hippocampus and thalamus. Conclusions Combination of glutathione and citrate can be one of the candidates for nanotoxicity alleviating drug against MNPs@SiO2(RITC) induced detrimental effect, including elevation of intracellular reactive oxygen species level, activation of microglia, and reduction in glucose uptake efficiency. In addition, our findings indicate that an integrated triple omics approach provides useful and sensitive toxicological assessment for nanoparticles and screening of drug for nanotoxicity. Graphical Abstract

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“…Interestingly, it was noted that neither the Alamar Blue test nor the neutral red assay showed a reduction in HUVEC-ST viability after treatment with PLA/EDTMP, PLGA/MDP, and PLA/MMT/TRA. As demonstrated by Helal-Neto et al 28 , HUVEC exposition to non-loaded NP does not interfere with their viability. Controversially, in experiments carried out with bacterial strains, Guedes et al 29 have indicated high MDP toxicity.…”

Section: Discussionmentioning

confidence: 69%

Disturbance of cellular homeostasis as a molecular risk evaluation of human endothelial cells exposed to nanoparticles

Wigner

Zieliński

Michlewska

et al. 2021

Sci Rep

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Even though application of nanoparticles in medicine seems to provide unique solutions for drug delivery and diagnosis diseases, understanding interactions between nanoscale materials and biological systems is imperative. Therefore, this study determined the effect of different types of nanoparticles (NPs) on human endothelial cells and examined the types of toxicity responses they can induce. Four different types of NPs were tested (PLA/MMT/TRASTUZUMAB, PLA/EDTMP, PLGA/MDP, and Pluronic F127 MICELLES), representing three putative areas of application: anticancer therapy, scintigraphy, and cosmetology. The experiments were performed on immortalized human umbilical vein endothelial cells (HUVEC-STs). Light contrast phase microscopy as well as cell viability assays showed that only Pluronic F127 MICELLES decreased the number of HUVEC-STs in contrast to PLA/MMT/TRASTUZUMAB, PLA/EDTMP, and PLGA/MDP NPs, which altered cell morphology, but not their confluency. The tested NPs induced not only DNA strand-breaks and alkali-labile sites, but also internucleosomal DNA fragmentation, visualized as a DNA ladder pattern typical of apoptosis. Moreover, generation of free radicals and subsequent mitochondrial membrane potential collapse showed the significance of free radical production during interactions between NPs and endothelial cells. High concentrations of NPs had different degrees of toxicity in human endothelial cells and affected cell proliferation, redox homeostasis, and triggered mitochondrial dysfunction.

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Molecular and Cellular Risk Assessment of Healthy Human Cells and Cancer Human Cells Exposed to Nanoparticles

Cited by 16 publications

References 74 publications

Radioactive gold nanocluster (198-AuNCs) showed inhibitory effects on cancer cells lines

Radioactive gold nanocluster (198-AuNCs) showed inhibitory effects on cancer cells lines

Silica-coated magnetic-nanoparticle-induced cytotoxicity is reduced in microglia by glutathione and citrate identified using integrated omics

Disturbance of cellular homeostasis as a molecular risk evaluation of human endothelial cells exposed to nanoparticles

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