Nanotoxicity of nanodiamond in two and three dimensional liver models

Khanal, Dipesh; Hau, Herman; Kondyurin, Alexey; Fu, Dong; Ramzan, Iqbal; Chrzanowski, Wojciech

doi:10.1504/ijnt.2017.082436

Cited by 10 publications

(5 citation statements)

References 48 publications

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“…Imaging of dry powders on AFM has always been a challenge, and many different strategies have been attempted in the past with limited success. Adhesives such as poly-Llysine, 31 polyethyleneimide, 32 and aminopropyltriethoxysilane 33 are used to immobilize particles on substrates such as metal discs, silicon wafers, and freshly cleaved mica. However, these methods are suited for immobilizing nanosize particles, and larger particles may move during AFM imaging due to insufficient adhesive strength.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

High Resolution Nanoscale Probing of Bacteriophages in an Inhalable Dry Powder Formulation for Pulmonary Infections

Khanal

Chang

Morales³

et al. 2019

Anal. Chem.

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Use of powder phage formulations for the treatment of multiple-drug-resistant pulmonary infections is gaining attention. To achieve therapeutic benefits, it is critical for phages to remain stable in the formulation. Assessment of phage stability relies on plaque assay (bioactivity), which requires powder samples to be reconstituted in liquid. The purpose of this study was to develop an innovative approach using photothermal-induced resonance-enhanced atomic force microscopy infrared spectroscopy (AFM-IR) to assess the presence of phages and investigate their protein conformation in the solid state. Staphylococcal phage S83 was spray-dried with lactose and sodium stearate using spray-drying. The phage powder recrystallized at 60% relative humidity (RH), so it was stored and handled below this RH. For the AFM-IR measurements, spray-dried Staphylococcal phage Sa83 powder was embedded in resin, followed by microtome sectioning. AFM-IR spectra collected from different regions within the microtomed sections revealed the presence of phage proteins with amide I and amide II bands at 1640 and 1550 cm–1, respectively. The phages were confirmed to be stable, as the plaque assay showed negligible titer reduction after spray-drying. Our results thus demonstrated the utility of AFM-IR for characterization of nanosized phages present in extremely low quantity in spray-dried particles. These biologically active phages were shown to retain their physical and chemical integrity in the spray-dried particles.

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Section: ■ Results and Discussionmentioning

confidence: 99%

High Resolution Nanoscale Probing of Bacteriophages in an Inhalable Dry Powder Formulation for Pulmonary Infections

Khanal

Chang

Morales³

et al. 2019

Anal. Chem.

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“…The majority of the results obtained from experiments carried out in vitro are inconclusive as they are generally based on 2D models that cannot adequately mimic the complexity of in vivo settings. On the contrary, the design of 3D cell culture models can be an important strategy to overcome this issue and better predict the biological response in vivo [185]. …”

Section: Discussionmentioning

confidence: 99%

Multifunctional nanodiamonds in regenerative medicine: Recent advances and future directions

Whitlow

Pacelli

Paul

2017

Journal of Controlled Release

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With recent advances in the field of nanomedicine, many new strategies have emerged for diagnosing and treating diseases. At the forefront of this multidisciplinary research, carbon nanomaterials have demonstrated unprecedented potential for a variety of regenerative medicine applications including novel drug delivery platforms that facilitate the localized and sustained release of therapeutics. Nanodiamonds (NDs) are a unique class of carbon nanoparticles that are gaining increasing attention for their biocompatibility, highly functional surfaces, optical properties, and robust physical properties. Their remarkable properties have established NDs as an invaluable regenerative medicine platform, with a broad range of clinically relevant applications ranging from targeted delivery systems for insoluble drugs, bioactive substrates for stem cells, and fluorescent probes for long-term tracking of cells and biomolecules in vitro and in vivo. This review introduces the synthesis techniques and the various routes of surface functionalization that allow for precise control over the properties of NDs. It also provides an in-depth overview of the current progress made towards the use of NDs in the fields of drug delivery, tissue engineering, and bioimaging. Their future outlook in regenerative medicine including the current clinical significance of NDs, as well as the challenges that must be overcome to successfully translate the reviewed technologies from research platforms to clinical therapies will also be discussed.

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“…The effect of NDs on cell growth and function in a 3D mini-liver model was quantified using ring closure and dot assays following previously published methodology (Khanal, et al, 2017, Timm, et al, 2013, Tseng, et al, 2015. In brief, cells were cultured overnight with magnetic nanoparticles (NanoShuttle−PL; Greiner Bio-One, USA) at a concentration of 8 μL/cm 2 .…”

Section: Cytotoxicity Of Nd In 3d Mini-liver Modelmentioning

confidence: 99%

“…The lack of measurable cytotoxicity in the first 24 h could also be related to sedimentation time of NDs and progressively increasing number of NDs that reached cells (Cohen, et al, 2013). Therefore, short-term experiments which are conducted for 24 h or less may not be conclusive and effective in testing NDs cytotoxicity (Khanal, et al, 2017, Yu, et al, 2005, Liu, et al, 2007, Schrand, et al, 2007. One solution could be measurements of intracellular concentrations of NDs that may provide additional insights into the toxicity of NDs.…”

Section: Nds Induce Ros-mediated Concentration-and Time-dependent Cymentioning

confidence: 99%

Biological impact of nanodiamond particles – label free, high-resolution methods for nanotoxicity assessment

et al. 2019

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Current methods for the assessment of nanoparticle safety that are based on 2D cell culture models and fluorescence-based assays, show limited sensitivity and they lack biomimicry. Consequently, the health risks associated with the use of many nanoparticles have not yet been established. There is a need to develop in vitro models that mimic physiology more accurately and enable high throughput assessment. There is also a need to set up new assay that offer high sensitivity and are label-free. Here we developed 'miniliver' models using scaffold-free bioprinting and used these models together with labelfree nanoscale techniques for the assessment of toxicity of nanodiamond produced by laser-assisted technology. Results showed that NDs induced cytotoxicity in a concentration and exposure-time dependent manner. The loss of cell function was confirmed by increased cell stiffness, decreased cell membrane barrier integrity and reduced cells mobility. We further showed that NDs elevated the production of reactive oxygen species and reduced cell viability. Our approach that combined mini-liver models with label-free high-resolution techniques showed improved sensitivity in toxicity assessment. Notably, this approach allowed for label-free semi-high throughput measurements of nanoparticlecell interactions thus could be considered as a complementary approach to currently used methods.

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Nanotoxicity of nanodiamond in two and three dimensional liver models

Cited by 10 publications

References 48 publications

High Resolution Nanoscale Probing of Bacteriophages in an Inhalable Dry Powder Formulation for Pulmonary Infections

High Resolution Nanoscale Probing of Bacteriophages in an Inhalable Dry Powder Formulation for Pulmonary Infections

Multifunctional nanodiamonds in regenerative medicine: Recent advances and future directions

Biological impact of nanodiamond particles – label free, high-resolution methods for nanotoxicity assessment

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