Fate of Cellulose Nanocrystal Aerosols Deposited on the Lung Cell Surface In Vitro

Abstract

When considering the inhalation of high-aspect ratio nanoparticles (HARN), the characterization of their specific interaction with lung cells is of fundamental importance to help categorize their potential hazard. The aim of the present study was to assess the interaction of cellulose nanocrystals (CNCs) with a multicellular in vitro model of the epithelial airway barrier following realistic aerosol exposure. Rhodamine-labeled CNCs isolated from cotton (cCNCs, 237 ± 118 × 29 ± 13 nm) and tunicate (t-CNCs, 2244 ± 1687 × 30 ± 8 nm) were found to display different uptake behaviors due to their length, although also dependent upon the applied concentration, when visualized by laser scanning microscopy. Interestingly, the longer t-CNCs were found to exhibit a lower clearance by the lung cell model compared to the shorter c-CNCs. This difference can be attributed to stronger fiber−fiber interactions between the t-CNCs. In conclusion, nanofiber length and concentration has a significant influence on their interaction with lung cells in vitro.

Enhanced Mechanical Properties in Cellulose Nanocrystal–Poly(oligoethylene glycol methacrylate) Injectable Nanocomposite Hydrogels through Control of Physical and Chemical Cross-Linking

“…27,28 Based on their demonstrated low cytotoxicity [29][30][31][32][33][34][35] they have also recently gained interest in biomedical applications including tissue engineering, drug delivery and bioimaging. 30,[36][37][38] To date, CNCs have been used as a reinforcing component in hydrogels 5 (primarily polyacrylamide-based materials [39][40][41] ) and other biocomposite materials including electrospun poly(lactic acid) 42 and cellulose fiber scaffolds.…”

A critical review of the current knowledge regarding the biological impact of nanocellulose

“…A sophisticated triple-cell co-culture model of the human epithelial tissue barrier (formulated of a layer of epithelial cells, complimented by human blood monocyte derived macrophages and dendritic cells on the apical and basolateral sides respectively) was used in a study that showed no significant cytotoxicity of two different CNC types isolated from cotton (170 ± 72 × 19 ± 7 nm) and tunicates (2.3 ± 1.4 µm × 31 ± 7 nm) that were deposited onto the cells in realistic doses (0.14 ± 0.04, 0.81 ± 0.03 and 1.57 ± 0.03 µg/cm 2 ) from aerosolized water-based suspensions [79, 80]. However, clearance, albeit based upon a dose, time and CNC-dependent manner, of deposited CNCs by macrophages was observed when cells were exposed to both of these types CNCs, with a lower efficiency associated with the tunicate CNCs (Fig.…”

“…However, clearance, albeit based upon a dose, time and CNC-dependent manner, of deposited CNCs by macrophages was observed when cells were exposed to both of these types CNCs, with a lower efficiency associated with the tunicate CNCs (Fig. 3) [79]. Jeong and co-workers used bacterial cellulose (BC; no dimensions given [81]) in in vitro experiments with human umbilical vein endothelial cells (HUVECs) [81].…”

Elucidating the Potential Biological Impact of Cellulose Nanocrystals

“…Whilst these models show a different biochemical/biomolecular response to monoculture systems (whether it be a similar trend, but different concentration-based effects, or a completely different biological effect) [100], there is still much debate and unknown as to how they correlate to the in vivo scenario, albeit efforts are underway to address this knowledge gap [101]. Such systems have recently been shown to be advantageous in determining the hazard posed by nanocellulose [47], as well as its interaction with cellular systems [102]. Table 2.…”

“…The use of state-of-the-art microscopy approaches will be necessary due to the innate difficulties in identifying nanocellulose within cellular structures. A recent study by Endes et al showed the possibility to achieve imaging of CNCs within cells by fluorescently labelling the nanocellulose used, with the assumption that small amounts of dye, in this case fluorescein, does not have any significant effect on the associated tests, such as uptake or cytotoxicity [102]. Analytical techniques should be sought out, which can directly identify cellulose, without the need of modification to easily identify nanocellulose inside cells so that a toxicodynamic approach can be undertaken.…”