Quantification of single-cell nanoparticle concentrations and the distribution of these concentrations in cell population

Rashkow, Jason Thomas; Patel, Sunny C.; Tappero, Ryan; Sitharaman, Balaji

doi:10.1098/rsif.2013.1152

Cited by 27 publications

(29 citation statements)

References 20 publications

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“…The importance of a large‐sized GNP and a high molar concentration has been demonstrated but no optimal size or distribution exists. The size of GNPs in the literature for both experimental and computational work can vary significantly and typically range from 10 to 100 nm . In terms of distribution within the cell, GNPs have been shown to be mostly distributed inside the cytoplasm with smaller particles having a higher probability of entering the nucleus .…”

Section: Methodsmentioning

confidence: 99%

Modeling gold nanoparticle radiosensitization using a clustering algorithm to quantitate DNA double‐strand breaks with mixed‐physics Monte Carlo simulation

Liu

Zhao

et al. 2019

Medical Physics

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Purpose: The radiosensitization properties of gold nanoparticles (GNPs) are investigated using a simple Geant4 cell model considering a realistic cell geometry and a clustering algorithm to characterize the number of DNA double-strand breaks (DSBs). Materials and methods: A mixed-physics approach is taken for accurate modeling of low-energy photon interactions in the different regions of the model using Geant4-DNA physics within the cell, and Livermore physics within gold. Density-based spatial clustering of applications with noise (DBSCAN), a clustering algorithm, is used to directly quantitate DNA DSBs after irradiation. The simulation was run using different sizes of GNPs, different distances of GNPs from the cell nucleus, and several combinations of these two conditions. Results: Four types of radiation were simulated in the work: 80-keV monoenergetic photons, 100-keV monoenergetic photons, a 250-kVp photon spectrum, and a 6-MV flattening filter free (FFF) photon spectrum. A variable enhancement in DSB yield, nucleus dose, and cell dose was observed when there are GNPs in the cell cytoplasm, and increases with larger GNPs and proximity to the nucleus. The distance of the GNPs from the nucleus has a large impact on the DSB yield and nucleus dose, but little to no effect on the cell dose. The cell dose enhancement factor of 80 keV photons varies from 1.037-1.125 at 0.2 µm for 30-100 nm GNPs to 1.040-1.127 at 4 lm. The DSB enhancement factor varies from 1.050 to 1.174 at 0.2 µm to a marginal effect of <1.01 at 4 lm. For 100 keV, the dose enhancement factor is from 1.142-1.470 at 0.2 µm to 1.106-1.371 at 4 lm. The DSB enhancement factor varies from 1.249-1.813 at 0.2 µm to almost no effect at 4 lm. For 250 kVp, the dose enhancement factor is from 1.117-1.393 at 0.2 lm to 1.110-1.342 at 4 lm. The DSB enhancement factor varies from 1.183-1.600 at 0.2 lm to a marginal effect of~1.03 at 4 lm. A 6-MV FFF shows a dose enhancement factor of 1.061-1.103 at 0.2 lm and 1.053-1.107 at 4 lm. The DSB yield varies from 1.070-1.143 at 0.2 lm to a marginal effect at 4 lm. Conclusion: The stark difference in behavior for DSB yield when compared to cell dose highlights the importance of evaluating more complex radiobiological quantities rather than dose alone when evaluating the radiosensitization properties from metallic nanomaterials. The nucleus dose showed similar characteristics to the DSB yield demonstrating the ability of the method to predict DNA damage and its relationship with nuclear dose. The proposed method provides a way to explore the radiobiological mechanisms of radiation-induced DNA damages, and it aids to evaluate the physical radiosensitization properties of GNP-aided radiotherapy, which can be easily combined with radiochemical DSB quantitation in order to better understand the intricate DNA damage induction mechanisms that are involved in GNP-aided radiotherapy.

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Section: Methodsmentioning

confidence: 99%

Modeling gold nanoparticle radiosensitization using a clustering algorithm to quantitate DNA double‐strand breaks with mixed‐physics Monte Carlo simulation

Liu

Zhao

et al. 2019

Medical Physics

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“…Inductively coupled plasma mass spectrometry (ICP-MS) is a common technique for absolute quantification of the cellular uptake of metal or metal oxide NPs. It offers high sensitivity and selectivity for elemental analysis [ 19 , 20 ]. Routinely it requires that cells are lysed before analysis.…”

Section: Introductionmentioning

confidence: 99%

Quantification and visualization of cellular uptake of TiO2 and Ag nanoparticles: comparison of different ICP-MS techniques

et al. 2016

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BackgroundSafety assessment of nanoparticles (NPs) requires techniques that are suitable to quantify tissue and cellular uptake of NPs. The most commonly applied techniques for this purpose are based on inductively coupled plasma mass spectrometry (ICP-MS). Here we apply and compare three different ICP-MS methods to investigate the cellular uptake of TiO2 (diameter 7 or 20 nm, respectively) and Ag (diameter 50 or 75 nm, respectively) NPs into differentiated mouse neuroblastoma cells (Neuro-2a cells). Cells were incubated with different amounts of the NPs. Thereafter they were either directly analyzed by laser ablation ICP-MS (LA-ICP-MS) or were lysed and lysates were analyzed by ICP-MS and by single particle ICP-MS (SP-ICP-MS).ResultsAll techniques confirmed that smaller particles were taken up to a higher extent when values were converted in an NP number-based dose metric. In contrast to ICP-MS and LA-ICP-MS, this measure is already directly provided through SP-ICP-MS. Analysis of NP size distribution in cell lysates by SP-ICP-MS indicates the formation of NP agglomerates inside cells. LA-ICP-MS imaging shows that some of the 75 nm Ag NPs seemed to be adsorbed onto the cell membranes and were not penetrating into the cells, while most of the 50 nm Ag NPs were internalized. LA-ICP-MS confirms high cell-to-cell variability for NP uptake.ConclusionsBased on our data we propose to combine different ICP-MS techniques in order to reliably determine the average NP mass and number concentrations, NP sizes and size distribution patterns as well as cell-to-cell variations in NP uptake and intracellular localization.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-016-0203-z) contains supplementary material, which is available to authorized users.

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“…Using model 20-30 nm TiO 2 spheres Rashkow showed a Gaussian distribution of titanium burdens within SK-BR-3 breast cancer cells with an average of 26 picomol Ti/cell after exposure (range 0-1.7 nanomol/cell). 27 Interestingly, none of the resulting intracellular TiO 2 particulates (100-8000 nm in size) become associated with the nucleus but some are present in intracellular vacuoles. Studies of related 'sheet-forms' of TiO 2 of dimensions 400 × 2 nm also induced the formation of vacuoles and triggered both paraptosis and apoptosis in mouse-derived white blood lung cells (MH-S) when so treated (24 h, 10-20 μg ml -1 , effective equivalent Ti concentration 0.1-0.2 μM; but only 20% growth inhibition was attained).…”

Section: Recent Findings In Titanium Anti-cancer 'Mode(s) Of Action'mentioning

confidence: 99%

Using titanium complexes to defeat cancer: the view from the shoulders of titans

2017

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When the first titanium complex with anticancer activity was identified in the 1970s, it was attractive, based on the presence of the dichloride unit in TiCl 2 Cp 2 (Cp = η-C 5 H 5 ) 2 , to assume its mode of biological action was closely aligned with cisplatin [cis-PtCl 2 (NH 3 ) 2 ]. Over the intervening 40 years however a far more complicated picture has arisen indicating multiple cellular mechanisms of cellular action can be triggered by titanium anti-cancer agents. This tutorial review aims to unpick the historical data and provide new researchers, without an explicit cancer biology background, a contemporary interpretation of both older and newer literature and to review the best techniques for attaining the identities of the biologically active titanium species and how these interact with the cancer cellular machinery. Key learning points(1) Understanding the problems in defining 'modes of action' in order to effectively design small molecular titanium-based therapeutic, agents when moving beyond simple 'structure vs. activity' correlations. (2) The dangers of over generalisation in historical 'mode of action' proposals in the absence of rigorous control experiments leading to proposals not fully in line with all (especially later) observations. (3) Titanium induced cellular morphology changes and contemporary thoughts on mode(s) of actionpresented in a way chemical scientists can 'get to grips with them' -understanding the hall marks of cellular death modes induced by titanium anti-cancer agents. (4) Modern tools for probing Ti-drug mechanisms of action, including: chiral probe complexes, added external proteins (transferrin, serum albumin); titanium solution speciation, and an overview of contemporary chemical-biology techniques of relevance to discovery of 'modes/mechanisms of action'.

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Quantification of single-cell nanoparticle concentrations and the distribution of these concentrations in cell population

Cited by 27 publications

References 20 publications

Modeling gold nanoparticle radiosensitization using a clustering algorithm to quantitate DNA double‐strand breaks with mixed‐physics Monte Carlo simulation

Modeling gold nanoparticle radiosensitization using a clustering algorithm to quantitate DNA double‐strand breaks with mixed‐physics Monte Carlo simulation

Quantification and visualization of cellular uptake of TiO2 and Ag nanoparticles: comparison of different ICP-MS techniques

Using titanium complexes to defeat cancer: the view from the shoulders of titans

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