On the toxicity of cellulose nanocrystals and nanofibrils in animal and cellular models

Ventura, Célia; Pinto, Fátima; Lourenço, Ana Filipa; Ferreira, Paulo J. T.; Louro, Henriqueta; Silva, Maria João

doi:10.1007/s10570-020-03176-9

On the toxicity of cellulose nanocrystals and nanofibrils in animal and cellular models

Review Paper
Published: 04 May 2020

Volume 27, pages 5509–5544, (2020)
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Cellulose Aims and scope Submit manuscript

Célia Ventura^1,2^na1,
Fátima Pinto¹^na1,
Ana Filipa Lourenço³,
Paulo J. T. Ferreira³,
Henriqueta Louro^1,2 &
…
Maria João Silva ORCID: orcid.org/0000-0002-6060-0716^1,2

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Abstract

The need for reaching environmental sustainability encourages research on new cellulose-based materials for a broad range of applications across many sectors of industry. Cellulosic nanomaterials obtained from different sources and with different functionalization are being developed with the purpose of its use in many applications, in pure and composite forms, from consumer products to pharmaceutics and healthcare products. Based on previous knowledge about the possible adverse health effects of other nanomaterials with high aspect ratio and biopersistency in body fluids, e.g., carbon nanotubes, it is expected that the nanometric size of nanocellulose will increase its toxicity as compared to that of bulk cellulose. Several toxicological studies have been performed, in vitro or in vivo, with the aim of predicting the health effects caused by exposure to nanocellulose. Ultimately, their goal is to reduce the risk to humans associated with unintentional environmental or occupational exposure, and the design of safe nanocellulose materials to be used, e.g., as carriers for drug delivery or other biomedical applications, as in wound dressing materials. This review intends to identify the toxicological effects that are elicited by nanocelluloses produced through a top-down approach from vegetal biomass, namely, cellulose nanocrystals and nanofibrils, and relate them with the physicochemical characteristics of nanocellulose. For this purpose, the article provides: (i) a brief review of the types and applications of cellulose nanomaterials; (ii) a comprehensive review of the literature reporting their biological impact, alongside to their specific physicochemical characteristics, in order to draw conclusions about their effects on human health.

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Abbreviations

AC:: Algal cellulose
AFM:: Atomic force microscopy
ATP:: Adenosine triphosphate
BAL:: Bronchoalveolar lavage
BC:: Bacterial cellulose
CMF:: Cellulose microfibril
CNC:: Cellulose nanocrystal
CNF:: Cellulose nanofibril
CNM:: Cellulose nanomaterial
CNT:: Carbon nanotube
DEG:: Differentially expressed genes
DNA:: Deoxyribonucleic acid
FITC:: Fluorescein isothiocyanate
GCSF:: Granulocyte colony-stimulating factor
GSH:: Glutathione
IL:: Interleukin
INF-γ:: Interferon-γ
LDH:: Lactate dehydrogenase
LPS:: Lipopolysaccharide
NLPR3:: NOD-like receptor pyrin domain-containing 3
NM:: Nanomaterial
MIP:: Macrophage inflammatory protein
MWCNT:: Multi-walled carbon nanotube
MTT:: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
OEL:: Occupational exposure limits
OM:: Optical microscopy
PBMNC:: Peripheral blood mononuclear cells
PDGF:: Glioma-derived growth factor
PMN:: Polymorphonuclear neutrophils
RANTES:: Regulated on activation, normal T cell expressed and secreted
REL:: Recommended exposure limits
ROS:: Reactive oxygen species
SEM:: Scanning electron microscopy
SH:: Protein sulfhydryl
TEM:: Transmission electron microscopy
TEMPO:: 2,2,6,6-Tetramethylpiperidine-1-oxyl radical
TNF-α:: Tumor necrosis factor α
TWA:: Time-weighted average

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Acknowledgments

The authors acknowledge CYTED network NANOCELIA (Transferencia Tecnológica sobre aplicaciones de nanocelulosa en iberoamérica). The work was funded by FCT/MCTES, Project ToxApp4NanoCELFI (PTDC/SAU-PUB/32587/2017) through national funds (PIDDAC), and co-funded by ToxOmics – Center for Toxicogenomics and Human Health (UID/BIM/00009/2013). Sara Teixeira is acknowledged for the binucleated cells photo.

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Célia Ventura and Fátima Pinto have contributed equally to this work.

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Department of Human Genetics, Instituto Nacional de Saúde Dr. Ricardo Jorge, Av. Padre Cruz, 1649-016, Lisbon, Portugal
Célia Ventura, Fátima Pinto, Henriqueta Louro & Maria João Silva
NOVA Medical School, ToxOmics - Centre for Toxicogenomics and Human Health, NOVA University of Lisbon, Lisbon, Portugal
Célia Ventura, Henriqueta Louro & Maria João Silva
CIEPQPF, Department of Chemical Engineering, Pólo II, University of Coimbra, Rua Silvo Lima, PT, 3030-790, Coimbra, Portugal
Ana Filipa Lourenço & Paulo J. T. Ferreira

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Célia Ventura
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Fátima Pinto
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Ana Filipa Lourenço
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Paulo J. T. Ferreira
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Henriqueta Louro
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Maria João Silva
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Ventura, C., Pinto, F., Lourenço, A.F. et al. On the toxicity of cellulose nanocrystals and nanofibrils in animal and cellular models. Cellulose 27, 5509–5544 (2020). https://doi.org/10.1007/s10570-020-03176-9

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Received: 10 December 2019
Accepted: 20 April 2020
Published: 04 May 2020
Issue Date: July 2020
DOI: https://doi.org/10.1007/s10570-020-03176-9

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