Toxicity assessment of aggregated/agglomerated cerium oxide nanoparticles in an in vitro 3D airway model: The influence of mucociliary clearance

Kuper, C. Frieke; Gröllers-Mulderij, Mariska; Maarschalkerweerd, T.V.P.; Meulendijks, Nicole; Reus, Astrid A.; Acker, Frédérique van; Beuken, Esther K. Zondervan-van den; Wouters, Mariëlle; Bijlsma, Sabina; Kooter, Ingeborg M.

doi:10.1016/j.tiv.2014.10.017

Cited by 54 publications

(19 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent reports showed potential clinical application and regenerative antioxidant properties of CeO 2 nanoparticles, some specifically engineered for biological applications with biocompatible surface coatings (Karakoti et al, ; Das et al, ; Madero‐Visbal et al, ; Chaudhury et al, ; Chigurupati et al, ; Das et al, ; Wason et al, ). Several research groups investigated the toxicological aspects of CeO 2 in in vitro and in vivo studies in formulations mimicking drug delivery for clinical application (Das et al, ; Demokritou et al, ; Morales et al, ; Schanen et al, ; Kumari et al, ; Yokel et al, ; Frieke Kuper et al, ). While studies have shown that industrially mimicking lung exposure and other exposure using commercial CeO 2 nanoparticles show inflammatory damage, in vitro studies of many CeO 2 nanoparticles engineered for biological application, show limited toxicity, indicating potential for all REO nanoparticles to be engineered to reduce toxicity.…”

Section: Introductionsupporting

confidence: 91%

Tissue deposition and toxicological effects of commercially significant rare earth oxide nanomaterials: Material and physical properties

et al. 2016

View full text Add to dashboard Cite

Rare earth oxide (REO) materials are found naturally in earth's crust and at the nanoscale these REO nanoparticles exhibit unique thermal, electrical, and physicochemical properties. REO nanoparticles are widely used in different industrial sectors for ceramics, glass polishing, metallurgy, lasers, and magnets. Recently, some of these REO nanoparticles have been identified for their potential application in medicine, including therapy, imaging, and diagnostics. Concurrent research into the REO nanomaterials' toxicities has also raised concern for their environmental impacts. The correlation of REO nanoparticles mediated toxicity with their physiochemical properties can help to design nanoparticles with minimal effect on the environment and living organisms. In vitro assay revealed toxicity toward Human squamous epithelial cell line (CCL30) and Human umbilical vascular endothelial cells (HUVEC) at a concentration of 100 µM and higher. In vivo results showed, with the exception of CeO and Gd O , most of the naoparticles did not clear or had minimum clearance (10-20%) from the system. Elevated levels of alanine transferase were seen for animals given each different nanoparticle, however the increases were not significant for CeO and Dy O . Nephrotoxicity was only seen in case of Dy O and Gd O . Lastly, histological examination revealed presence of swollen hepatocytes which further confirms toxicity of the commercial REO nanomaterials. The in vivo toxicity is mainly due to excessive tissue deposition (70-90%) due to the commercial REO nanoparticles' poor physical properties (shape, stability, and extent of agglomeration). Therefore, optimization of nanoparticles physical properties is very important. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 904-917, 2017.

show abstract

Section: Introductionsupporting

confidence: 91%

Tissue deposition and toxicological effects of commercially significant rare earth oxide nanomaterials: Material and physical properties

et al. 2016

View full text Add to dashboard Cite

show abstract

“…These advantages include fully differentiated epithelium (including basal, goblet, and ciliated cells), a mucus layer covering the epithelial cells, cilia beating, functional tight junction formation, and preservation of homeostatic state up to 1 year (Huang, Wiszniewski, & Constant, ). Thanks to these unique features, MucilAir™ models have been successfully used to discriminate between substance with low and high absorption in humans (Reus et al, ), to distinguish the respiratory sensitizers from dermal sensitizers (Huang et al, ), and they also have been partially explored for NPs interactions studies (Beaver et al, ; Frieke Kuper et al, ). MucilAir™ models are composed by primary human cells isolated from the nasal cavity, the trachea or the bronchus.…”

Section: Discussionmentioning

confidence: 99%

The curious case of how mimicking physiological complexity in in vitro models of the human respiratory system influences the inflammatory responses. A preliminary study focused on gold nanoparticles

Movia

Cristo

Alnemari

et al. 2017

J of Interdiscip Nanomed

View full text Add to dashboard Cite

Environmental and biomedical nanoparticles can pose potential health risks to the human respiratory system by inducing severe lung inflammation. The aim of this case study is to present a comparison of the inflammatory response in four in vitro models of the human lung epithelium, differing by composition and/or culturing substrates, when exposed to gold nanoparticles (AuNPs). Three in vitro models of lung adenocarcinoma (A549) cells and a commercially available three-dimensional (3D) culture (MucilAir ™ ) were tested.The models were exposed to AuNPs for 3, 6, and 24 h. AuNPs internalisation was investigated by confocal, electron microscopy, and Raman spectroscopy. Enzyme-Linked Immuno-Sorbent Assay (ELISA) was used for quantifying the secretion of the inflammatory mediator Interleukin-6 (IL-6) following exposure to AuNPs. Finally, a microfluidic approach was developed in-house to investigate whether pro-inflammatory mediators present in supernatants harvested from the AuNPs-treated cell cultures could trigger monocyte activation. Our results demonstrated that AuNPs were internalised only in submerged cultures grown on glass substrates. Nevertheless, AuNPs internalisation did not trigger a significant IL-6 secretion. Significant amounts of IL-6 were secreted by AuNPs-treated mono-cultures grown on Transwell ™ inserts, triggering monocyte activation in dynamic microfluidic experiments. AuNPs did not induce IL-6 secretion in co-cultures and MucilAir ™

show abstract

“…Besides that, ready‐to‐use in vitro models such as MucilAir TM and EpiAirway TM , which utilized the ALI technique, are now increasingly being used for toxicity and drug screening of inhaled nanomaterials. Frieke Kuper et al found that ALI culture can reflect the local toxicity of CeO 2 and ZnO nanoparticles observed in in vivo studies …”

Section: The Relevance Of 3d In Vitro Models For Nanomedicine Studiesmentioning

confidence: 99%

Reality Check for Nanomaterial‐Mediated Therapy with 3D Biomimetic Culture Systems

Tay

Muthu

Chia

et al. 2016

Adv Funct Materials

View full text Add to dashboard Cite

The recent progresses in tissue engineering and nanomaterial‐based therapeutics/theranostics have led to the ever increasing utilization of 3D in vitro experimental models as the bona fide culture systems to evaluate the therapeutic/theranostic effects of nanomedicine. Compared to the use of conventional 2D culture platforms, 3D biomimetic cultures offer unmatched advantages as relevant physiological and pathological elements can be incorporated to allow better characterization of the engineered bio‐nanomaterials in the targeted tissue‐specific microenvironment. In this Feature Article, the current state‐of‐the‐art 3D in vitro models that have been developed for the evaluation of biosafety and efficacy of nano‐ therapeutics/theranostics targeting the colon, blood–brain barrier (BBB), lungs, skin tumor models to bridge the nanomedicine bench to pre‐clinical ravine are reviewed. Furthermore, the critical physicochemical parameters of the bio‐nanomaterials that govern its transport and biodistribution in a complex 3D microenvironment will be highlighted. The major challenges and future prospects of evaluating nanomedicine in the third dimension will also be discussed.

show abstract

Toxicity assessment of aggregated/agglomerated cerium oxide nanoparticles in an in vitro 3D airway model: The influence of mucociliary clearance

Cited by 54 publications

References 28 publications

Tissue deposition and toxicological effects of commercially significant rare earth oxide nanomaterials: Material and physical properties

Tissue deposition and toxicological effects of commercially significant rare earth oxide nanomaterials: Material and physical properties

The curious case of how mimicking physiological complexity in in vitro models of the human respiratory system influences the inflammatory responses. A preliminary study focused on gold nanoparticles

Reality Check for Nanomaterial‐Mediated Therapy with 3D Biomimetic Culture Systems

Contact Info

Product

Resources

About