In vitro immune and redox response induced by cationic cellulose-based nanomaterials.

Cellulose nanocrystals (CNCs) display remarkable strength and physicochemical properties with significant potential applications. To better understand the potential adjuvanticity of a nanomaterial, it is important to investigate the extent of the immunological response, the mechanisms by which they elicit this response, and how this response is associated with their physicochemical characteristics. In this study, we investigated the potential mechanisms of immunomodulation and redox activity of two chemically related cationic CNC derivatives (CNC-METAC-1B and CNC-METAC-2B), using human peripheral blood mononuclear cells and mouse macrophage cells (J774A.1). Our data demonstrated that the biological effects caused by these nanomaterials occurred mainly with short term exposure. We observed opposite immunomodulatory activity between the tested nanomaterials. CNC-METAC-2B, induced IL-1ß secretion at 2 h while CNC-METAC-1B decreased it at 24 h of treatment. In addition, both nanomaterials caused more noticeable increases in mitochondrial reactive oxygen species (ROS) at early time. The differences in apparent sizes of the two cationic nanomaterials could explain, at least in part, the discrepancies in biological effects, despite their closely related surface charges. This work provides initial insights about the complexity of the in vitro mechanism of action of these nanomaterials as well as foundation knowledge for the development of cationic CNCs as potential immunomodulators.

Vascular and Blood Compatibility of Engineered Cationic Cellulose Nanocrystals in Cell-Based Assays.

An emerging interest regarding nanoparticles (NPs) concerns their potential immunomodulatory and pro-inflammatory activities, as well as their impact in the circulatory system. These biological activities of NPs can be related to the intensity and type of the responses, which can raise concerns about adverse side effects and limit the biomedical applicability of these nanomaterials. Therefore, the purpose of this study was to investigate the impact of a library of cationic cellulose nanocrystals (CNCs) in the human blood and endothelial cells using cell-based assays. First, we evaluated whether the cationic CNCs would cause hemolysis and aggregation or alteration on the morphology of red blood cells (RBC). We observed that although these nanomaterials did not alter RBC morphology or cause aggregation, at 24 h exposure, a mild hemolysis was detected mainly with unmodified CNCs. Then, we analyzed the effect of various concentrations of CNCs on the cell viability of human umbilical vein endothelial cells (HUVECs) in a time-dependent manner. None of the cationic CNCs caused a dose-response decrease in the cell viability of HUVEC at 24 h or 48 h of exposure. The findings of this study, together with the immunomodulatory properties of these cationic CNCs previously published, support the development of engineered cationic CNCs for biomedical applications, in particular as vaccine nanoadjuvants.