Synthetic Strategies for the Fabrication of Cationic Surface-Modified Cellulose Nanocrystals

Cellulose nanocrystals (CNCs) are renewable nanosized materials with exceptional physicochemical properties that continue to garner a high level of attention in both industry and academia for their potential high-end material applications. These rod-shaped CNCs are appealing due to their non-toxic, carbohydrate-based chemical structure, large surface area, and the presence of ample surface hydroxyl groups for chemical surface modifications. CNCs, generally prepared from sulfuric acid-mediated hydrolysis of native cellulose, display an anionic surface that has been exploited for a number of applications. However, several recent studies showed the importance of CNCs’ surface charge reversal towards the design of functional cationic CNCs. Cationization of CNCs could further open up other innovative applications, in particular, bioapplications such as gene and drug delivery, vaccine adjuvants, and tissue engineering. This mini-review focuses mainly on the recent covalent synthetic methods for the design and fabrication of cationic CNCs as well as their potential bioapplications

Self-assembled rosette nanotubes and poly(2-hydroxyethyl methacrylate) hydrogels promote skin cell functions

The next generation skin of wound healing materials should stimulate skin regeneration by actively promoting appropriate cellular adhesion and proliferation. As materials with novel self-assembling and solidification properties when transitioning from room to body temperatures, rosette nanotubes (RNTs) may be such a proactive material. RNTs resemble naturally occurring nanostructures in the skin (such as collagen and keratin) assembling with noncovalent forces in physiological environments. Presenting desirable bioactive properties, RNTs have been used for various tissue engineering applications including increasing in vivo bone and cartilage regeneration. The objective of the current in vitro study was, for the first time, to improve properties of a commonly used hydrogel (poly(2-hydroxyethyl methacrylate) or pHEMA) for skin regeneration by incorporating one type of novel self-assembled RNTs, called TBL. Results showed for the first time increased keratinocyte and fibroblast proliferation on hydrogels coated with TBLs compared to those not coated with TBL. In this manner, this study provides the first evidence that TBL RNTs are promising for wound healing applications due to their optimal cytocompatibility, solidification, and mechanical properties and, thus, should be further studied for such applications. \ua9 2013 Wiley Periodicals, Inc.Peer reviewed: YesNRC publication: Ye

Cationic cellulose nanocrystals : synthesis, characterization and cytotoxicity studies

Cellulose nanocrystals (CNCs) have emerged as a new class of renewable material for various applications due to their remarkable properties and commercialization prospect. The relative low density, expected low cost, non-toxic character, uniform nanosize distribution, high aspect ratios, high surface area, thermal properties and high modulus of elasticity make CNCs attractive nanomaterials that recently prompted the industrial production of CNCs in North America. Surface functionalization of CNCs continues to be an exciting area of research for the design of novel CNC-based materials. In this work, we report the synthesis, characterization and cytotoxicity studies of novel cationic surface modified CNC derivatives. The negative surface of CNC was rendered positive after grafting with cationic polymers via surface-initiated living radical polymerization method. The modified CNCs were characterized by both spectroscopic and microscopic techniques. Their cytotoxicity effects were evaluated using MTT assay in two cell lines such as mouse macrophages (J774.A1) and human breast cancer (MCF7). Preliminary studies indicated that only one of the modified CNCs caused significant decrease in J774.A1 cell viability (50%), at the highest concentration tested (100 \u3bcg/mL). However this concentration is well above of what would be applicable for biomedical purposes. MCF7 cells were not affected by any of the cationic CNCs at any concentration. A detailed cytotoxicity study is currently underway to fully understand the interaction of these cationic CNCs with the biological systems for possible bio-inspired applications.Peer reviewed: YesNRC publication: Ye

Chiromers : conformation driven mirror image supramolecular chirality isomerism identified in a new class of helical rosette nanotubes

Rosette nanotubes are biologically inspired nanostructures, formed through the hierarchical organization of a hybrid DNA base analogue (G 27C), which features hydrogen-bonding arrays of guanine and cytosine. Several twin-G 27C motifs functionalized with chiral moieties, which undergo a self-assembly process under methanolic and aqueous conditions to produce helical rosette nanotubes (RNTs), were synthesized and characterized. The built-in molecular chirality in the twin-G 27C building blocks led to the supramolecular chirality exhibited by the RNTs, as evidenced by the CD activity. Depending on the motifs and environmental conditions, mirror-image supramolecular chirality due to absolute molecular chirality, solvent-induced and structure-dependent supramolecular chirality inversion, and pH-controlled chiroptical switching were observed.Peer reviewed: YesNRC publication: Ye

Cationic Poly(2-aminoethylmethacrylate) and Poly(<i>N</i>‑(2-aminoethylmethacrylamide) Modified Cellulose Nanocrystals: Synthesis, Characterization, and Cytotoxicity

Cellulose nanocrystals (CNCs) continue to gain increasing attention in the materials community as sustainable nanoparticles with unique chemical and mechanical properties. Their nanoscale dimensions, biocompatibility, biodegradability, large surface area, and low toxicity make them promising materials for biomedical applications. Here, we disclose a facile synthesis of poly­(2-aminoethylmethacrylate) (poly­(AEM)) and poly­(<i>N</i>-(2-aminoethylmethacrylamide) (poly­(AEMA)) CNC brushes via the surface-initiated single-electron-transfer living radical polymerization technique. The resulting modified CNCs were characterized for their chemical and morphological features using a combination of analytical, spectroscopic, and microscopic techniques. Zeta potential measurements indicated a positive surface charge, and further proof of the cationic nature was confirmed by gold deposition as evidenced by electron microscopy. The cytotoxicity of these cationic modified CNCs was evaluated utilizing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in two different cell lines, J774A1 (mouse monocyte cells) and MCF-7 (human breast adenocarcinoma cells). The results indicated that none of the cationic modified CNCs decreased cell viability at low concentrations, which could be suitable for biomedical applications

Mechanistic insight into the induction of cellular immune responses by encapsulated and admixed archaeosome-based vaccine formulations

Archaeosomes are liposomes formulated using total polar lipids (TPLs) or semi-synthetic glycolipids derived from archaea. Conventional archaeosomes with entrapped antigen exhibit robust adjuvant activity as demonstrated by increased antigen-specific humoral and cell-mediated responses and enhanced protective immunity in various murine infection and cancer models. However, antigen entrapment efficiency can vary greatly resulting in antigen loss during formulation and variable antigen:lipid ratios. In order to circumvent this, we recently developed an admixed archaeosome formulation composed of a single semi-synthetic archaeal lipid (SLA, sulfated lactosylarchaeol) which can induce similarly robust adjuvant activity as an encapsulated formulation. Herein, we evaluate and compare the mechanisms involved in the induction of early innate and antigen-specific responses by both admixed (Adm) and encapsulated (Enc) SLA archaeosomes. We demonstrate that both archaeosome formulations result in increased immune cell infiltration, enhanced antigen retention at injection site and increased antigen uptake by antigen-presenting cells and other immune cell types, including neutrophils and monocytes following intramuscular injection to mice using ovalbumin as a model antigen. In vitro studies demonstrate SLA in either formulation is preferentially taken up by macrophages. Although the encapsulated formulation was better able to induce antigen-specific CD8+ T cell activation by dendritic cells in vitro, both encapsulated and admixed formulations gave equivalently enhanced protection from tumor challenge when tested in vivo using a B16-OVA melanoma model. Despite some differences in the immunostimulatory profile relative to the SLA (Enc) formulation, SLA (Adm) induces strong in vivo immunogenicity and efficacy, while offering an ease of formulation

The Synergistic Effects of Sulfated Lactosyl Archaeol Archaeosomes When Combined with Different Adjuvants in a Murine Model

Archaeosomes, composed of sulfated lactosyl archaeol (SLA) glycolipids, have been proven to be an effective vaccine adjuvant in multiple preclinical models of infectious disease or cancer. SLA archaeosomes are a promising adjuvant candidate due to their ability to strongly stimulate both humoral and cytotoxic immune responses when simply admixed with an antigen. In the present study, we evaluated whether the adjuvant effects of SLA archaeosomes could be further enhanced when combined with other adjuvants. SLA archaeosomes were co-administered with five different Toll-like Receptor (TLR) agonists or the saponin QS-21 using ovalbumin as a model antigen in mice. Both humoral and cellular immune responses were greatly enhanced compared to either adjuvant alone when SLA archaeosomes were combined with either the TLR3 agonist poly(I:C) or the TLR9 agonist CpG. These results were also confirmed in a separate study using Hepatitis B surface antigen (HBsAg) and support the further evaluation of these adjuvant combinations

Sulfated Lactosyl Archaeol Archaeosomes Synergize with Poly(I:C) to Enhance the Immunogenicity and Efficacy of a Synthetic Long Peptide-Based Vaccine in a Melanoma Tumor Model

Cancer remains a leading cause of morbidity and mortality worldwide. While novel treatments have improved survival outcomes for some patients, new treatment modalities/platforms are needed to combat a wider variety of tumor types. Cancer vaccines harness the power of the immune system to generate targeted tumor-specific immune responses. Liposomes composed of glycolipids derived from archaea (i.e., archaeosomes) have been shown to be potent adjuvants, inducing robust, long-lasting humoral and cell-mediated immune responses to a variety of antigens. Herein, we evaluated the ability of archaeosomes composed of sulfated lactosyl archaeol (SLA), a semi-synthetic archaeal glycolipid, to enhance the immunogenicity of a synthetic long peptide-based vaccine formulation containing the dominant CD8+ T cell epitope, SIINFEKL, from the weakly immunogenic model antigen ovalbumin. One advantage of immunizing with long peptides is the ability to include multiple epitopes, for example, the long peptide antigen was also designed to include the immediately adjacent CD4+ epitope, TEWTSSNVMEER. SLA archaeosomes were tested alone or in combination with the toll-like receptor 3 (TLR3) agonist Poly(I:C). Overall, SLA archaeosomes synergized strongly with Poly(I:C) to induce robust antigen-specific CD8+ T cell responses, which were highly functional in an in vivo cytolytic assay. Furthermore, immunization with this vaccine formulation suppressed tumor growth and extended mouse survival in a mouse melanoma tumor model. Overall, the combination of SLA archaeosomes and Poly(I:C) appears to be a promising adjuvant system when used along with long peptide-based antigens targeting cancer