A Framework to Account for Sedimentation and Diffusion in Particle–Cell Interactions

Cui, Jiwei; Faria, Matthew; Björnmalm, Mattias; Ju, Yi; Suma, Tomoya; Gunawan, Sylvia T.; Richardson, Joseph J.; Heidari, Hamed; Bals, Sara; Crampin, Edmund J.; Caruso, Frank

doi:10.1021/acs.langmuir.6b01634

Cited by 51 publications

(82 citation statements)

References 45 publications

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“…The decreased association between nanoparticles and HUVECs under flow conditions may be related to the reduced exposure of these nanoparticles to cells even though the same number of particles had been introduced . In flow conditions, spherical nanoparticles tend to follow the cell medium streamlines when passing through the SMN; while in static conditions, all nanoparticles have a tendency to settle on the cell surfaces due to gravity . That said, the trend of association between HUVECs and PISA nanoparticles of different surface chemistries (i.e., COOH < PEG < Me < TA) is similar when comparing between static and flow conditions.…”

Section: Resultsmentioning

confidence: 98%

Elucidating the Influences of Size, Surface Chemistry, and Dynamic Flow on Cellular Association of Nanoparticles Made by Polymerization‐Induced Self‐Assembly

Khor

Pilkington

et al. 2018

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The size and surface chemistry of nanoparticles dictate their interactions with biological systems. However, it remains unclear how these key physicochemical properties affect the cellular association of nanoparticles under dynamic flow conditions encountered in human vascular networks. Here, the facile synthesis of novel fluorescent nanoparticles with tunable sizes and surface chemistries and their association with primary human umbilical vein endothelial cells (HUVECs) is reported. First, a one-pot polymerization-induced self-assembly (PISA) methodology is developed to covalently incorporate a commercially available fluorescent dye into the nanoparticle core and tune nanoparticle size and surface chemistry. To characterize cellular association under flow, HUVECs are cultured onto the surface of a synthetic microvascular network embedded in a microfluidic device (SynVivo, INC). Interestingly, increasing the size of carboxylic acid-functionalized nanoparticles leads to higher cellular association under static conditions but lower cellular association under flow conditions, whereas increasing the size of tertiary amine-decorated nanoparticles results in a higher level of cellular association, under both static and flow conditions. These findings provide new insights into the interactions between polymeric nanomaterials and endothelial cells. Altogether, this work establishes innovative methods for the facile synthesis and biological characterization of polymeric nanomaterials for various potential applications.

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Section: Resultsmentioning

confidence: 98%

Elucidating the Influences of Size, Surface Chemistry, and Dynamic Flow on Cellular Association of Nanoparticles Made by Polymerization‐Induced Self‐Assembly

Khor

Pilkington

et al. 2018

Small

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“…Conventional cell uptake or cytotoxicity study are normally performed on 2D cell monolayer or 3D tumor spheroids in a well plate where the culture medium is static, and this might lead to false positive results, because sedimentation of nanoparticles may occur when the culture medium is static . Therefore, drug evaluation under flow conditions might be more relevant as it better mimics the real in vivo conditions.…”

Section: Resultsmentioning

confidence: 99%

A Microfluidic Tumor‐on‐a‐Chip for Assessing Multifunctional Liposomes' Tumor Targeting and Anticancer Efficacy

Ran

Wang

Hou

et al. 2019

Adv Healthcare Materials

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Two principal methods for cancer drug testing are widely used, namely, in vitro 2D cell monolayers and in vivo animal models. In vitro 2D culture systems are simple and convenient but are unable to capture the complexity of biological processes. Animal models are costly, time‐consuming, and often fail to replicate human activity. Here a microfluidic tumor‐on‐a‐chip (TOC) model designed for assessing multifunctional liposome cancer targeting and efficacy is presented. The TOC device contains three sets of hemispheric wells with different sizes for tumor spheroid formation and evaluation of liposomes under a controlled flow condition. There is good agreement between time‐elapsed tumor targeting of fluorescent liposomes in the TOC model and in in vivo mouse models. Evaluation of the anticancer efficacy of four PTX‐loaded liposome formulations shows that compared to 2D cell monolayers and 3D tumor spheroid models, the TOC model better predicts the in vivo anticancer efficacy of targeted liposomes. Lastly, the TOC model is used to assess the effects of flow rates and tumor size on treatment outcome. This study demonstrates that the TOC model provides a convenient and powerful platform for rapid and reliable cancer drug evaluation.

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“…S3). [40][41][42] Both particle types were fluorescently labelled with Alexa Fluor 488 (AF488) before the silica templates were removed with buffered hydrofluoric acid. Particles were characterized using optical microscopy, fluorescence microscopy, electron microscopy, microelectrophoresis (to calculate zeta (ζ)potentials), and flow cytometry.…”

Section: Methodsmentioning

confidence: 99%

Interactions between circulating nanoengineered polymer particles and extracellular matrix components in vitro

et al. 2017

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The extracellular matrix (ECM) that surrounds cells in vivo represents a biological barrier for nanomaterials in biomedicine. Herein, we present a system for investigating the interactions between circulating polymer particles and ECM components in vitro using a commercially available flow-based device. We use this system to show how material-dependent interactions of two different particle types-one assembled using poly(ethylene glycol) (PEG) and one prepared using poly(methacrylic acid) (PMA)-affect their interactions with basement membrane extracts during in vitro circulation, with PEG particles remaining in circulation longer than PMA particles. Further, by comparing macroporous hyaluronic acid gel constructs (typically used for tissue engineering) with basement membrane extracts, we show that scaffold-effects (porosity and surface chemistry) impact on circulation time in vitro. The presented system is simple and modular, and can be used to rapidly screen fundamental interactions of engineered particles with biologically relevant microenvironments under flow-conditions.

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A Framework to Account for Sedimentation and Diffusion in Particle–Cell Interactions

Cited by 51 publications

References 45 publications

Elucidating the Influences of Size, Surface Chemistry, and Dynamic Flow on Cellular Association of Nanoparticles Made by Polymerization‐Induced Self‐Assembly

Elucidating the Influences of Size, Surface Chemistry, and Dynamic Flow on Cellular Association of Nanoparticles Made by Polymerization‐Induced Self‐Assembly

A Microfluidic Tumor‐on‐a‐Chip for Assessing Multifunctional Liposomes' Tumor Targeting and Anticancer Efficacy

Interactions between circulating nanoengineered polymer particles and extracellular matrix components in vitro

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