Synthesis and Cytotoxicity Studies of Wood-Based Cationic Cellulose Nanocrystals as Potential Immunomodulators

Imtiaz, Yusha; Tuga, Beza; Smith, Christopher W.; Rabideau, Alexander; Nguyen, Long H.; Liu, Yali; Hrapovic, Sabahudin; Ckless, Karina; Sunasee, Rajesh

doi:10.3390/nano10081603

Cited by 18 publications

(13 citation statements)

References 37 publications

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“…The hemolytic effect of the unmodified CNCs on the RBC lysis could be attributed, at least in part, to the surface chemistry and reactivity between unmodified and modified CNCs. Unmodified CNCs displayed a negative surface charge (−34.8 ± 2.16 mV) and the derivatized CNCs showed a cationic surface charge ranging between +31.8 ± 2.89 and +45.0 ± 1.44 mV [ 20 ]. In addition to the charge differences, the reactivity of unmodified CNCs is also different from the derivatized counterparts.…”

Section: Resultsmentioning

confidence: 99%

“…RBC aggregation and morphology together with RBC lysis are important parameters to assess the biocompatibility of nanomaterials [ 22 ]. None of the CNCs induced RBC aggregation at short ( Figure 2 A,B) or long exposure ( Figure 3 A,B), despite their cationic surface charges [ 20 ] and cationic polymers such as polyethyleneimine (PEI) that are well known to cause RBC aggregation [ 28 ]. The positive control, PEG 1 mg/mL, induced strong RBC aggregation in both short and long exposure ( Figure 2 and Figure 3 C, respectively).…”

Section: Resultsmentioning

confidence: 99%

“…The unmodified CNCs possess a negative surface charge due to the presence of the sulfate half-ester groups. CNCs conjugated with the cationic polymers [2-(methacryloyloxy)ethyl]trimethylammonium chloride (METAC) and 2-aminoethyl methacrylate hydrochloride (AEM) were synthesized via surface-initiated single electron transfer living radical polymerization and characterized using analytical, spectroscopy and microscopy techniques as described in our recent publication [ 20 ]. The chemical structures of unmodified CNCs and engineered cationic CNCs (also referred to as modified CNCs) are depicted in Scheme 1 and their respective compositions, apparent particle sizes, and zeta potentials are illustrated in Table S1 .…”

Section: Methodsmentioning

confidence: 99%

“…This new library of cationic CNCs was evaluated using three different cell-based assays and relevant immune cells, including mouse cell lines and human peripheral blood mononuclear cells (PBMCs). Overall, we demonstrated that these cellulose-based nanomaterials present very low cytotoxicity in all our tested experimental conditions [ 20 ]. Given that these cationic cellulose-based nanomaterials have the potential to be developed as immunomodulators and therefore vaccine nanoadjuvants, it is paramount that all aspects of their interactions with biological systems must be evaluated.…”

Section: Introductionmentioning

confidence: 99%

“…In fact, the immunostimulatory activity of cationic CNCs was first described in our previous work in which we found that they induced the secretion of the inflammatory cytokine, IL-1β, in mouse and human macrophage cells [ 18 , 19 ]. Recently, we successfully expanded the library of cationic CNCs by engineering the surface of CNCs with poly[2-(methacryloyloxy)ethyl]trimethylammonium chloride (METAC) and poly(aminoethyl methacrylate hydrochloride (AEM)) possessing pendant cationic groups (+NMe 3 and +NH 3 respectively)[ 20 ]. By changing the proportion of initiators (2-bromoisobutyryl bromide, Brib) and monomers (METAC and AEM) during the polymerization process, we obtained a series of cationic CNCs with different surface charges and hydrodynamic sizes.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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Natural Biomaterials from Biodiversity for Healthcare Applications

Insuasti-Cruz

Suárez-Jaramillo

Mena

et al. 2021

Adv Healthcare Materials

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Natural biomaterials originating during the growth cycles of all living organisms have been used for many applications. They span from bioinert to bioactive materials including bioinspired ones. As they exhibit an increasing degree of sophistication, natural biomaterials have proven suitable to address the needs of the healthcare sector. Here the different natural healthcare biomaterials, their biodiversity sources, properties, and promising healthcare applications are reviewed. The variability of their properties as a result of considered species and their habitat is also discussed. Finally, some limitations of natural biomaterials are discussed and possible future developments are provided as more natural biomaterials are yet to be discovered and studied.

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Virus pH‐Dependent Interactions with Cationically Modified Cellulose and Their Application in Water Filtration

Watts

Maniura‐Weber

Siqueira³

et al. 2021

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responsible for numerous deaths and epidemics in high-income as well as emerging countries. [2] Water treatment reduces the impact of such pathogens on populations [2a] but efficient low-cost solutions for virus removal are not straightforward due to this contaminant's nanometer scale size. Filtration of viruses by conventional size-exclusion requires pore sizes of 20 nm or smaller, resulting in the need of a high overhead pressure and an increased running cost. [3] Virus removal from drinking water by membrane filtration has been recently reviewed. [4] Moreover, membrane filtration separates contaminants only on the top surface of the filter leading to fouling problems and a need for backflushing and chemical cleaning, [5] hence increased running costs.As opposed to size-exclusion, depth filtration relies on the adsorption of contaminants to the filter material. [6] The main pathogens of interest, Rotavirus and Norovirus, are negatively charged within the W.H.O and U.S.E.P.A. recommended drinking water pH range, from 6.5 to 8.5. [7] Hence, these viruses and positively charged materials can interact electrostatically through charge attraction. Tailoring the filter material to interact with the contaminants is a key parameter to achieve efficient removal in depth filtration. Related to this, membranes have been surface-modified with cationic polymers, promoting the adsorption of negatively charged viruses. [8] However, the drawback of this approach is the relatively small membrane surface at which the separation occurs. Ceramic depth filters modified with metal nanoparticles have allowed the removal of nanosize contaminants including viruses. [9] However, the potential leaching of toxic metal from the filter may be a major risk. [10] This study demonstrates the development of a sustainable adsorption-based filter material from the abundant biopolymer cellulose.Cellulose is a promising raw material for filter design: it is widely available, cheap, biodegradable, renewable, nontoxic and its chemical modification is straightforward. [11] These characteristics make it a well-used material for membranes in water treatment processes as well as biotechnology processes. [12] The vast majority of these studies focus, for particle separation, on cellulose in size-exclusion membranes. For example, removal of swine influenza virus (SIV), a 130 nm spherical lipid enveloped virus, [13] has been achieved by size-exclusion using nanofibrilated cellulose (NFC) membrane. [14] However, the problematic waterborne pathogenic Norovirus and Rotavirus are smaller than Norovirus and Rotavirus are among the pathogens causing a large number of disease outbreaks due to contaminated water. These viruses are nanoscale particles that are difficult to remove by common filtration approaches which are based on physical size exclusion, and require adsorption-based filtration methods. This study reports the pH-responsive interactions of viruses with cationic-modified nanocellulose and demonstrates a filter material that adsorbs nanoscale viruse...

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Synthesis and Cytotoxicity Studies of Wood-Based Cationic Cellulose Nanocrystals as Potential Immunomodulators

Cited by 18 publications

References 37 publications

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

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

Natural Biomaterials from Biodiversity for Healthcare Applications

Virus pH‐Dependent Interactions with Cationically Modified Cellulose and Their Application in Water Filtration

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