Problems and challenges in the development and validation of human cell-based assays to determine nanoparticle-induced immunomodulatory effects

Nanotechnology is having a tremendous impact on our society. However, societal concerns about human safety under nanoparticle exposure may derail the broad application of this promising technology. Nanoparticles may enter the human body via various routes, including respiratory pathways, the digestive tract, skin contact, intravenous injection, and implantation. After absorption, nanoparticles are carried to distal organs by the bloodstream and the lymphatic system. During this process, they interact with biological molecules and perturb physiological systems. Although some ingested or absorbed nanoparticles are eliminated, others remain in the body for a long time. The human body is composed of multiple systems that work together to maintain physiological homeostasis. The unexpected invasion of these systems by nanoparticles disturbs normal cell signaling, impairs cell and organ functions, and may even cause pathological disorders. This review examines the comprehensive health risks of exposure to nanoparticles by discussing how nanoparticles perturb various physiological systems as revealed by animal studies. The potential toxicity of nanoparticles to each physiological system and the implications of disrupting the balance among systems are emphasized.

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“…163 All of these problems will need to be resolved satisfactorily to ensure the reliable assessment of immune nanotoxicity.…”

Section: 152mentioning

confidence: 99%

Perturbation of physiological systems by nanoparticles

et al. 2014

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“…These assays have also been used for NPs toxicity evaluation [7][8][9][10]. Although plate-based assays offer several advantages (e.g., fast, easy, and reproducible), accumulating data show that NP interference with plate-based assay substrates can lead to erroneous data and provide little correlation with in vivo studies [11][12][13][14]. Some of NP properties that were reported to interfere with viability plate-based assays are surface charge, agglomeration/aggregation, hydrophobicity, and optical or magnetic properties [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Viability and Proliferation Profiles on Macrophages Treated with Silica Nanoparticles In Vitro via Plate-Based, Flow Cytometry, and Coulter Counter Assays

Bancos

Tsai

Hackley

et al. 2012

ISRN Nanotechnology

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Nanoparticles (NPs) are known to interfere with many high-throughput cell viability and cell proliferation assays, which complicates the assessment of their potential toxic effects. The aim of this study was to compare viability and proliferation results for colloidal silica (SiO 2 NP; 7 nm) in the RAW 264.7 mouse macrophage cell line using three different techniques: plate-based assays, flow cytometry analysis, and Coulter counter assays. Our data indicate that CellTiter-Blue, XTT, and CyQuant plate-based assays show increased values over control at low SiO 2 NPs concentrations (0.001-0.01 g/L). SiO 2 NPs show little-to-no interference with flow cytometry and Coulter counter assays, which not only were more reliable in determining cell viability and proliferation at low concentrations in vitro, but also identified changes in cell granularity and size that were not captured by the plate-based assays. At high SiO 2 NP concentrations (1 g/L) all techniques indicated cytotoxicity. In conclusion, flow cytometry and Coulter counter identified new cellular features, and flow cytometry offered more flexibility in analyzing the viability and proliferation profile of SiO 2 NP-treated RAW 264.7 cells.

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“…[20][21][22] However, little attention has been given to the use of LAL to prepare NPs for biomedical applications especially the toxicity, biodistribution, and clearance of these probes. [23][24][25][26] Characterization of the immune response to these agents is particularly relevant, 27,28 especially in vivo. [28][29][30] These studies are important to understand the relationship between NP structure and toxicity and thus provide the rational suggestions on the design of contrast agents in the future.…”

Section: Introductionmentioning

confidence: 99%

Toxicity evaluation of Gd2O3@SiO2 nanoparticles prepared by laser ablation in liquid as MRI contrast agents in vivo

Tian¹,

Yang²,

Yang³

et al. 2014

IJN

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Poor toxicity characterization is one obstacle to the clinical deployment of Gd 2 O 3 @ SiO 2 core-shell nanoparticles (Gd-NPs) for use as magnetic resonance (MR) imaging contrast agents. To date, there is no systematic toxicity data available for Gd-NPs prepared by laser ablation in liquid. In this article, we systematically studied the Gd-NPs’ cytotoxicity, apoptosis in vitro, immunotoxicity, blood circulation half-life, biodistribution and excretion in vivo, as well as pharmacodynamics. The results show the toxicity, and in vivo MR data show that these NPs are a good contrast agent for preclinical applications. No significant differences were found in cell viability, apoptosis , and immunotoxicity between our Gd-NPs and Gd in a DTPA (diethylenetriaminepentaacetic acid) chelator. Biodistribution data reveal a greater accumulation of the Gd-NPs in the liver, spleen, lung, and tumor than in the kidney, heart, and brain. Approximately 50% of the Gd is excreted via the hepatobiliary system within 4 weeks. Furthermore, dynamic contrast-enhanced T1-weighted MR images of xenografted murine tumors were obtained after intravenous administration of the Gd-NPs. Collectively, the single step preparation of Gd-NPs by laser ablation in liquid produces particles with satisfactory cytotoxicity, minimal immunotoxicity, and efficient MR contrast. This may lead to their utility as molecular imaging contrast agents in MR imaging for cancer diagnosis.

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Problems and challenges in the development and validation of human cell-based assays to determine nanoparticle-induced immunomodulatory effects

Cited by 184 publications

References 49 publications

Perturbation of physiological systems by nanoparticles

Perturbation of physiological systems by nanoparticles

Evaluation of Viability and Proliferation Profiles on Macrophages Treated with Silica Nanoparticles In Vitro via Plate-Based, Flow Cytometry, and Coulter Counter Assays

Toxicity evaluation of Gd2O3@SiO2 nanoparticles prepared by laser ablation in liquid as MRI contrast agents in vivo

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