The role of biological fluid and dynamic flow in the behavior and cellular interactions of gold nanoparticles

Abstract

Background: Due to their distinctive physicochemical properties, nanoparticles (NPs) have proven to be extremely advantageous for product and application development, but are also capable of inducing detrimental outcomes in biological systems. Standard in vitro methodologies are currently the primary means for evaluating NP safety, as vast quantities of particles exist that require appraisal. However, cell-based models are plagued by the fact that they are not representative of complex physiological systems. The need for a more accurate exposure model is highlighted by the fact that NP behavior and subsequent bioresponses are highly dependent upon their surroundings. Therefore, standard in vitro models will likely produce inaccurate NP behavioral analyses and erroneous safety results. As such, the goal of this study was to develop an enhanced in vitro model for NP evaluation that retained the advantages of cell culture, but implemented the key physiological variables of accurate biological fluid and dynamic flow.Results: In this study, a cellular microenvironment was modeled and created after an inhalation exposure scenario. This system comprised of A549 lung epithelial cells, artificial alveolar fluid (AAF), and biologically accurate dynamic flow. Under the influence of microenvironment variables, tannic acid coated gold NPs (AuNPs) displayed modulated physicochemical characteristics, including increased agglomeration, disruption of the spectral signature, and decreased rate of ionic dissolution. Furthermore, AuNP deposition efficiency, internalization patterns, and the nanocellular interface varied as a function of fluid composition and flow condition. AAF incubation simultaneously influenced both AuNPs and cellular behavior, through excessive NP agglomeration and alteration to A549 morphology. Dynamic flow targeted the nano-cellular interface, with differential responses including modified deposition, internalization patterns, and cellular elongation. Lastly, the biocompatibility of the system was verified to ensure cellular health following AAF exposure and fluid dynamics. Conclusions:This study confirmed the feasibility of improving standard in vitro models through the incorporation of physiological variables. Utilization of this enhanced system demonstrated that to elucidate true NP behavior and accurately gauge their cellular interactions, assessments should be carried out in a more complex and relevant biological exposure model.

A comparative study of the biodurability and persistence of gold, silver and titanium dioxide nanoparticles using the continuous flow through system

“…These subtle differences are likely due to that the functionalized AuNPs are coated with polyethylene glycol (PEG) then functionalized with the carboxyl and amine functional groups. Consequently, PEG provides electro steric stabilizing thereby preventing the particles from combining to form agglomerates as a result, they remain monodispersed [44,45]. However, the citrate on the citrate stabilized AuNPs is just a stabilizing agent which can be easily displaced from the NP surface as a result it is easier to from agglomerates once the stabilizing agent is removed.…”

Breathing in vitro: Designs and applications of engineered lung models

“…Finally, a prevalent choice for the provision of medium flow is through the use of bioreactors with a tubing system and pumps. [28][29][30][31][32][33][34] In these models, well inserts are typically cultured with epithelial and endothelial cells, on the apical and basal sides, respectively. The endothelial compartment is connected to the tubing system and thus sustained by media flow, which can be controlled to regulate the level of shear stress on the cells.…”

“…31 Toxicology studies have also been performed to evaluate the effects of NPs (e.g. gold NPs), 34 or other airborne materials such as pollen. 33 These examples illustrate that the use of flow systems is relevant for studies, where the role of shear stress on cell responses is assessed, and for absorption studies, where more complex kinetics and dynamics are considered.…”

“…No No Cell-NP interaction Breitner et al 34 Yes No Patho-physiological stretching models, stem cell differentiation Grek et al, 26 Jeans et al, 32 Ghaedi et al, 27 Blume et al, 33 Box et al 31 Yes Toxicology Tarkington et al, 43 Tippe et al, 60 199 Long et al, 200 Benam et al, 201,204 Li et al, 205 Jain et al 202…”

Modification of the protein corona–nanoparticle complex by physiological factors

“…This flow rate was specifically targeted due to the fact that standard physiological velocities, including those for arteries, arterioles, capillaries, and venules, range between 0.2 and 1.0 cm/s [20]. To generate flow in a 24-well cell culture dish the tubing ends were inserted and secured through precisely drilled holes in the plate lid, as previously performed [26]. For dynamic evaluation, the AuNPs were resuspended in media at a concentration of 25 µg/mL then allowed to reside in the flowing system for 24 hours at 37 °C.…”