Tuning payload delivery in tumour cylindroids using gold nanoparticles

Kim, Byoung-Jin; Han, Gang; Toley, Bhushan J.; Kim, Chaekyu; Rotello, Vincent M.; Forbes, Neil S.

doi:10.1038/nnano.2010.58

Cited by 448 publications

(373 citation statements)

References 40 publications

(48 reference statements)

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“…We could not find previous D data for dextrans in rBM gels. Instead, the reported diffusivity of gold nanoparticles in rBM was ~0.110 -6 cm 2 /s [34], which is very close to our D values at the highest R H (Fig. 2A).…”

Section: Discussionsupporting

confidence: 88%

“…Our spectrophotometer-based assay in which the intensity of fluorescently-labelled diffusing particles was analyzed within the diffusion layer minimized the effects of photobleaching in the widely used FITC-dextrans, and reported apparent diffusivity values that were ~15% lower in average than those obtained with FRAP. Comparing our D values with those reported elsewhere for similar dextrans and gels revealed a relative difference of ≤30% for COLI gels and dense FIB [5,34,35]. We could not find previous D data for dextrans in rBM gels.…”

Section: Discussioncontrasting

confidence: 50%

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A spectrophotometer-based diffusivity assay reveals that diffusion hindrance of small molecules in extracellular matrix gels used in 3D cultures is dominated by viscous effects

Galgoczy

Pastor

Colom

et al. 2014

Colloids and Surfaces B: Biointerfaces

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Please cite this article as: R. Galgoczy, I. Pastor, A. Colom, A. Giménez, F. Mas, J. Alcaraz, A spectrophotometer-based diffusivity assay reveals that diffusion hindrance of small molecules in extracellular matrix gels used in 3D cultures is dominated by viscous effects, Colloids and Surfaces B: Biointerfaces (2014), http://dx.doi.org/10. 1016/j.colsurfb.2014.05.017 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThe design of 3D culture studies remains challenging due to the limited understanding of extracellular matrix (ECM)-dependent hindered diffusion and the lack of simple diffusivity assays. To address these limitations, we set up a cost-effective diffusivity assay based on a Transwell plate and the spectrophotometer of a Microplate Reader, which are readily accessible to cell biology groups. The spectrophotometer-based assay was used to assess the apparent diffusivity D of FITC-dextrans with molecular weight (4-70 kDa) spanning the physiological range of signaling factors in a panel of acellular ECM gels including Matrigel, fibrin and type I collagen. Despite their technical differences, D data exhibited ~15% relative difference with respect to FRAP measurements. Our results revealed that diffusion hindrance of small particles is controlled by the enhanced viscosity of the ECM gel in conformance with the Stokes-Einstein equation rather than by geometrical factors. Moreover, we provided a strong rationale that the enhanced ECM viscosity is largely contributed to by unassembled ECM macromolecules. We also reported that gels with the lowest D exhibited diffusion hindrance closest to the large physiologic hindrance of brain tissue, which has a typical pore size much smaller than ECM gels.Conversely, sparse gels (≤ 1 mg/ml), which are extensively used in 3D cultures, failed to reproduce the hindered diffusion of tissues, thereby supporting that dense (but not sparse) ECM gels are suitable tissue surrogates in terms of macromolecular transport. Finally, the consequences of reduced diffusivity in terms of optimizing the design of 3D culture experiments were addressed in detail.

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Section: Discussionsupporting

confidence: 88%

Section: Discussioncontrasting

confidence: 50%

A spectrophotometer-based diffusivity assay reveals that diffusion hindrance of small molecules in extracellular matrix gels used in 3D cultures is dominated by viscous effects

Galgoczy

Pastor

Colom

et al. 2014

Colloids and Surfaces B: Biointerfaces

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“…Chemicals used were HAuCl 4 ·3 H 2 O (SigmaAldrich; ACS reagent), triphenylphosphine (Alfa Aesar; 99+ wt%), NaBH 4 [Aldrich; purum pro analysi (p.a. )], BF 3 ·OEt 2 (Aldrich), H 2 SO 4 (Grüssing; p.a.…”

Section: Methodsmentioning

confidence: 99%

Differential hERG ion channel activity of ultrasmall gold nanoparticles

Leifert

Pan

Kinkeldey

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Understanding the mechanism of toxicity of nanomaterials remains a challenge with respect to both mechanisms involved and product regulation. Here we show toxicity of ultrasmall gold nanoparticles (AuNPs). Depending on the ligand chemistry, 1.4-nm-diameter AuNPs failed electrophysiology-based safety testing using human embryonic kidney cell line 293 cells expressing human ether-á-go-go-Related gene ( hERG ), a Food and Drug Administration-established drug safety test. In patch-clamp experiments, phosphine-stabilized AuNPs irreversibly blocked hERG channels, whereas thiol-stabilized AuNPs of similar size had no effect in vitro, and neither particle blocked the channel in vivo. We conclude that safety regulations may need to be reevaluated and adapted to reflect the fact that the binding modality of surface functional groups becomes a relevant parameter for the design of nanoscale bioactive compounds.

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“…4−6 Therefore, there is a pressing need to gain a thorough understanding of the fundamental interactions between NPs and cells, which can include electrostatic, hydrophobic, and hydrogen-bonding interactions. 7,8 Surface charge is related to biological behaviors of NPs, such as tissue diffusing, 9 biodistribution, 10−13 cell uptake, 11,14−25 cytotoxicity, 14,22,23,25−29 and protein binding. 16,30−33 Electrostatic interaction between NPs and cells is very important in applications such as gene delivery, 34−36 cell uptake enhancing, 18 and endosome escaping.…”

Section: ■ Introductionmentioning

confidence: 99%

Effective Surface Charge Density Determines the Electrostatic Attraction between Nanoparticles and Cells

Zhou

et al. 2012

J. Phys. Chem. C

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ABSTRACT:We examine the origin of the electrostatic attraction between nanoparticle (NP) and cells by synthesizing a NP array with a continuous change in surface charge density (SCD). This attraction does not show a linear and continuous change, but a sharp increase as the positive SCD increases. The results of zeta potential measurements of the naked and protein bound NPs reveal that excessive charges on surface ligands are partially shielded, and the noncovalent protein bindings do not influence NP−cell electrostatic interactions. The effective SCD on the outmost layer of NPs determined the electrostatic attraction between NPs and cells

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Tuning payload delivery in tumour cylindroids using gold nanoparticles

Cited by 448 publications

References 40 publications

A spectrophotometer-based diffusivity assay reveals that diffusion hindrance of small molecules in extracellular matrix gels used in 3D cultures is dominated by viscous effects

A spectrophotometer-based diffusivity assay reveals that diffusion hindrance of small molecules in extracellular matrix gels used in 3D cultures is dominated by viscous effects

Differential hERG ion channel activity of ultrasmall gold nanoparticles

Effective Surface Charge Density Determines the Electrostatic Attraction between Nanoparticles and Cells

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