Anionic Surface Charge Research Articles

Dexamethasone simulates the anticancer effect of nano-formulated paclitaxel in breast cancer cells.

Although the chemosensitizing effect of Dexamethasone (DEX) and its ability to increase the sensitivity of breast cancer cells to chemotherapy were previously reported, this study aimed to explore how far cotreatment of breast cancer cells with paclitaxel (PTX) and DEX mimics the anticancer effect of nanoformulated PTX. To establish this goal, PTX was nanoformulated with poly (lactic-co-glycolic acid) (PLGA) and the nanoparticles (PTX-NPs) were physically authenticated. Breast cancer cells (MCF-7) were treated with PTX or PTX-NPs in presence or absence of low concentration (10nM) of DEX. Cells viability (assessed by MTT assay), apoptosis (assessed by flow cytometry) and the expression of PTX resistance gene (TRX1) and PTX metabolizing genes (CYP2C8 and CYP3A4) were investigated. The results showed that nanoformulated PTX was validated by nano-size assessment, increased the anionic surface charge and prober conjugation with the biodegradable carrier (PLGA), as indicated by the FTIR spectroscopy. Initially, the IC50 value of PTX was 19.3μg/ml and cotreatment with DEX minimized it to 5.22μg/ml, whereas PTX-NPs alone inhibited cell proliferation with IC50 6.67μg/ml. Also, in presence of DEX, PTX-NPs further decreased the IC50 to 5μg/ml. In parallel, DEX has increased the responsiveness of cells to PTX without potentiating its apoptotic effect. Moreover, the glucocorticoid (with PTX or PTX-NPs) downregulated TXR1 gene by 26% (P<0.01) and 28.4% (P<0.05) respectively. Similarly, the mRNA level of CYP3A4 significantly decreased in presence of DEX. The main PTX metabolizing gene CYP2C8, in contrast, was upregulated, especially in cells cotreated with PTX/DEX (P<0.001). Conclusively, the study reports that cotreatment of breast cancer cells with submolar concentration of DEX acts as similar as the nanoformulated PTX, possibly through its modulatory effects on the expression of the main PTX metabolizing gene (CYP2C8) and downregulating Taxol resistance gene.

Fabrication of multifunctional microfibrous and nanofibrous cellulose carriers and comparison of cell adhesion and spreading potential on them

Fibrous biomaterials have received much attention in tissue engineering and regenerative medicine due to their morphology, resembling extracellular matrix. In comparison to synthetic fibers, cellulose based fibers have interesting properties for cellular applications such as biodegradability, biocompatibility, simple preparation and their potential for chemical modification. Among cellulose derivatives, carboxymethyl cellulose and quaternized cellulose are the most important and valuable cellulose ethers which have anionic and cationic surface charge. In this research, we report the fabrication of multifunctional cellulose microfibrous and nanofibrous scaffolds and the comparison of adhesion and spreading potential of human fibroblast cell on them. The fabricated fibrous scaffolds were characterized by several instrumental techniques. The results showed that multifunctional cellulose nanofibers and microfiber had 8.6 and 8.2 mV surface potential, 7.1 and 6.8 MPa tensile strength, 560 and 510 MPa Young modules, 610 and 595% water uptake and 41o and 44o contact angle, respectively. The MTT assay showed that proliferation of fibroblast cells was enhanced in nanofibrous, compared to microfibrous mat. The SEM analysis of fixed cells on scaffolds showed that cells spreading on nanofibrous samples became more noticeable than microfibrous ones.

Development of Vaccines with Self-assembled Carriers That Deliver Drugs to Target Organs

I have developed novel ternary complexes of various vaccines with cationic materials and anionic polymers. Plasmid DNA (pDNA) encoding firefly luciferase was used as a model drug to form adequate ternary complexes. Cationic binary complexes were constructed using pDNA and polyethylenimine, and these binary complexes were coated with various anionic polymers to form ternary complexes. These ternary complexes significantly improved cytotoxicity and aggregation with erythrocytes in comparison to the binary complexes. On the other hand, most of those ternary complexes showed little in vitro transgene efficiency because of their anionic surface charge. γ-Polyglutamic acid (γ-PGA)-ternary complexes, however, demonstrated high in vitro transgene efficiency. After the intravenous administration of γ-PGA-ternary complexes to mice, extremely high gene expression was detected in the marginal zone of the spleen, which is rich in antigen-presenting cells. This spleen-specific phenomenon of γ-PGA-ternary complexes appeared to be suited to DNA vaccines against cancer. I therefore examined the preventive effect of γ-PGA-ternary complexes containing pUb-M, a pDNA encoding melanoma surface antigen, against melanoma-bearing mice. Vaccinations of γ-PGA-ternary complexes into mice significantly suppressed the tumor growth of B16-F10 melanoma cells subcutaneously injected into the mice. In the same manner, vaccinations of γ-PGA-ternary complexes containing ovalbumin (OVA) completely suppressed the growth of E.G7-OVA cells expressing OVA. These results strongly suggest that γ-PGA-ternary complexes are useful in the manufacture of specific tumor vaccines.

Formulation and Intracellular Trafficking of Lipid-Drug Conjugate Nanoparticles Containing a Hydrophilic Antitubercular Drug for Improved Intracellular Delivery to Human Macrophages.

Isoniazid is an important first-line antitubercular drug used in the treatment of all major clinical manifestations of tuberculosis, including both pulmonary and cerebral diseases. However, it is associated with significant drawbacks due to its inherent hydrophilic nature, including poor gut permeability and an inability to cross the lipophilic blood–brain barrier, which, in turn, limit its clinical efficacy. We hypothesized that the addition of a hydrophobic moiety to this molecule would help overcome these limitations and improve its bioavailability in the bloodstream. Therefore, we designed a stable, covalently linked lipid–drug conjugate of isoniazid with a short lipid chain of stearoyl chloride. Further, lipid–drug conjugate nanoparticles were synthesized from the bulk lipid–drug conjugate by a cold high-pressure homogenization method enabled by the optimized use of aqueous surfactants. The nanoparticle formulation was characterized systematically using in vitro physicochemical analytical methods, including atomic force microscopy, transmission electron microscopy, differential scanning calorimetry, X-ray diffraction, attenuated total reflectance, particle size, ζ-potential, and drug release studies, and the mechanism of drug release kinetics. These investigations revealed that the lipid–drug conjugate nanoparticles were loaded with an appreciable amount of isoniazid conjugate (92.73 ± 6.31% w/w). The prepared lipid–drug conjugate nanoparticles displayed a uniform shape with a smooth surface having a particle size of 124.60 ± 5.56 nm. In vitro drug release studies showed sustained release up to 72 h in a phosphate-buffered solution at pH 7.4. The release profile fitted to various known models of release kinetics revealed that the Higuchi model of diffusion kinetics was the best-fitting model (R2 = 0.9929). In addition, confocal studies showed efficient uptake of lipid–drug conjugate nanoparticles by THP-1 macrophages presumably because of increased lipophilicity and anionic surface charge. This was followed by progressive intracellular trafficking into endosomal and lysosomal vesicles and colocalization with intravesicular compartmental proteins associated with mycobacterium tuberculosis pathogenesis, including CD63, LAMP-2, EEA1, and Rab11. The developed lipid–drug conjugate nanoparticles, therefore, displayed significant ability to improve the intracellular delivery of a highly water-soluble drug such as isoniazid.

Influence of size and surface acidity of silica nanoparticles on inhibition of the formation damage by bentonite-free water-based drilling fluids. Part I: nanofluid design based on fluid-nanoparticle interaction

The study aims to evaluate the effect of size and surface acidity of synthesised silica (SiO2) nanoparticles in a bentonite-free water-based drilling fluid (BFWBM) to minimise its impact on formation damage by filtration volume control and mudcake thickness reduction. Nanoparticles were synthesised through the sol-gel method, and the surfaces were modified through the incipient impregnation technique using acidic and basic treatments. The nanoparticles were characterised by dynamic light scattering (DLS), Fourier transforms infrared spectroscopy (FTIR) and zeta potential measurements. Drilling fluid properties in the presence and absence of nanoparticles were evaluated through the analysis of pH, density, solid content, rheology, and static filtration tests at high pressure and temperature. Drilling fluids were described as shear-thinning fluids under the rheological model of Herschel-Bulkley. The smallest nanoparticles (Si11) contributed to the highest filtration and mudcake thickness reduction. Hence, these were modified to obtain a different surface charge. Silica nanoparticles modified with the acidic treatment (Si11A) in drilling fluids showed the highest reduction of the filtration volume and mud cake thickness with values of −22% and −65%, respectively. Also, the filtration volume appeared to be a function of the zeta potential of nanoparticles that were investigated, for the highest zeta potential value, SiA −48.66 mV @ pH 10, the filtration volume is lower. SiO2 nanoparticles in a BFWBM reduce the filtration volume due to their nanometric size occupying empty spaces in the mudcake and promoting the repulsive forces avoiding the flocculation of the drilling fluid thanks to the anionic surface charge. This study provides a wider landscape about the role of the size and surface acidity of the SiO2 nanoparticles in the stability and dispersion of the BFWBM.

Effect of Surface Charges on Oral Absorption of Intact Solid Lipid Nanoparticles.

Surface charge is a crucial factor that determines the in vivo behaviors of drug nanocarriers following administration via different routes. However, there is still a lack of comprehensive knowledge of how surface charges affect the in vivo behaviors of particles, especially for oral delivery. In this study, solid lipid nanoparticles (SLNs), as model drug nanocarriers, are modified to bear either anionic, cationic, or net neutral surface charges. The effect of surface charges on oral absorption of intact SLNs was investigated by tracking the in vivo transport of the particles. The fluorescent bioimaging strategy exploits the aggregation-caused quenching property to discriminate the particles. Both in vitro and in vivo lipolysis studies confirm slowed-down lipolysis by anionic charges in comparison with both unmodified and net neutral SLNs but accelerated degradation by cationic charges. The scanning of ex vivo tissues and organs reveals limited absorption of unmodified SLNs into the circulation. Nevertheless, all three types of surface charge modifications are able to enhance the oral absorption of intact SLNs with the fastest and highest absorption observed for net neutral SLNs, possibly owing to promoted mucus penetration. Anionic SLNs, though repulsed by the mucus layer, show the second highest absorption owing to enhanced lymphatic transport. The efficacy of cationic charge modification is less significant due to entrapment and retention in mucus layers as well as increased lability to lipolysis. In conclusion, surface charges may serve as initiators to guide the in vivo behaviors and enhance the oral absorption of intact SLNs.

Lactic acid‐mediated isolation of alpha‐, beta‐ and kappa‐casein fractions by isoelectric precipitation coupled with cold extraction from defatted cow milk

The present study focused on the isolation of individual caseins (α, β and κ) from defatted cow's milk using lactic acid‐mediated isoelectric precipitation coupled with cold extraction technique, followed by purification using sucrose‐based density gradient centrifugation method. In vitro characterisation of the isolated casein fractions confirmed preservation of micellar morphology throughout the experimental conditions with anionic surface charge and wider particle size range. The RP‐HPLC analysis showed a peak at retention time of 25.13 min and 27.84 min for α‐casein and β‐casein, respectively. Results confirmed isolation of pure casein fractions from cow's milk which could serve as a rich source of bioactive peptides for nutraceutical/pharmaceutical applications.

Molecular-Level Insight into the Interactions of DNA/Polycation Complexes with Model Cell Membranes.

The interactions of DNA/polycation complexes (polyplexes) with cell membranes are crucial for understanding the molecular mechanisms behind polycation-mediated delivery of nucleic acid therapeutics into the target cells. In this study, we employed both biased and unbiased atomic-scale computer simulations to get an insight into such interactions. To this end, we considered complexes of DNA with linear polyethylenimine (PEI) with various polycation contents, ranging from an almost fully neutralized DNA to a highly overcharged polyplex. Our findings clearly show that the free energy gradually increases when a polyplex approaches the surface of a zwitterionic (neutral) phospholipid membrane from bulk water, implying the lack of attractive polyplex/membrane interactions. Remarkably, overcharging of DNA molecules by polycations enhances the repulsion between the polyplex and the zwitterionic lipid membrane. The observed repulsion is most likely driven by the dehydration of a polyplex upon its partitioning into the zwitterionic lipid membrane as well as by the loss of conformational entropy of PEI chains. We also demonstrate that cationic polymer chains are able to protect DNA from the dehydration as well as from contacts with lipid molecules. Interestingly, the absence of local minima in the free energy profiles does not exclude transient weak adsorption of a polyplex on the zwitterionic membrane surface. We show that such spontaneous adsorption can indeed be initiated by the interactions of loose polycation chains of the polyplex with polar head groups of lipids. Overall, our computational findings contribute considerably to the understanding of the initial stages in polycation-mediated DNA transfection. In particular, we demonstrate that a zwitterionic lipid bilayer represents an energetic barrier for polyplexes, so that a proper model of the cell membrane should account for the anionic surface charge of the membrane (e.g., due to the presence of proteoglycans).

In vivo imaging and biodistribution of near infrared dye loaded brain-metastatic-breast-cancer-cell-membrane coated polymeric nanoparticles

Brain metastatic breast cancer is challenging to treat due to the presence of the blood-brain barrier (BBB) and a lack of ability to target precisely. Most drugs fail to cross the BBB limiting their effectiveness. To combat this problem, a brain metastatic breast cancer cell (MDA-MB-831) membrane-coated polymeric nanoparticle (CCNP) was synthesized. The small size (∼70 nm) and anionic surface charge (−20 mV) achieved during formulation allowed for high penetration and retention in the brain when compared to the PEGylated polymeric nanoparticle alone (mPEG-PLGA or NP). Doxorubicin-loaded CCNP showed high preferential cytotoxicity in vitro. Live (4–120 h) and ex vivo near-infrared imaging in nude mice showed extended circulation and retention of CCNP compared to uncoated nanoparticles. These data indicate that drug/dye-loaded CCNPs demonstrate excellent potential for cancer theranostics of brain metastatic breast tumors.

Co-assembled Ca2+ Alginate-Sulfate Nanoparticles for Intracellular Plasmid DNA Delivery

Successful gene therapy requires the development of suitable carriers for the selective and efficient delivery of genes to specific target cells, with minimal toxicity. In this work, we present a non-viral vector for gene delivery composed of biocompatible materials, CaCl2, plasmid DNA and the semi-synthetic anionic biopolymer alginate sulfate (AlgS), which spontaneously co-assembled to form nanoparticles (NPs). The NPs were characterized with a slightly anionic surface charge (Zeta potential [ζ] = −14 mV), an average size of 270 nm, and their suspension was stable for several days with no aggregation. X-ray photoelectron spectroscopy (XPS) validated their ternary composition, and it elucidated the molecular interactions among Ca2+, the plasmid DNA, and the AlgS. Efficient cellular uptake (>80%), associated with potent GFP gene expression (22%–35%), was observed across multiple cell types: primary rat neonatal cardiac fibroblasts, human breast cancer cell line, and human hepatocellular carcinoma cells. The uptake mechanism of the NPs was studied using imaging flow cytometry and shown to be via active, clathrin-mediated endocytosis, as chemical inhibition of this pathway significantly reduced EGFP expression. The NPs were cytocompatible and did not activate the T lymphocytes in human peripheral blood mononuclear cells. Proof of concept for the efficacy of these NPs as a carrier in cancer gene therapy was demonstrated for Diphtheria Toxin Fragment A (DT-A), resulting in abrogation of protein synthesis and cell death in the human breast cancer cell line. Collectively, our results show that the developed AlgS-Ca2+-plasmid DNA (pDNA) NPs may be used as an effective non-viral carrier for pDNA.

Polyelectrolyte-activated carbon composite electrodes for inverted membrane capacitive deionization (iMCDI)

A new way of desalination using capacitive deionization (CDI) technology is by inverting the potential profile (inverted capacitive deionization iCDI). This means ions adsorb to the electrodes at 0 V and desorb when biasing the electrodes to larger potential differences. Previously, this operation was achieved by preparing electrode materials with anionic and cationic surface charges. Here we show, as a novelty, that an inverted CDI operation is also possible with conventional activated carbon electrodes when used in combination with ion exchange membranes (inverted membrane capacitive deionization iMCDI). Further we show that, the salt separation could be increased to 5.2 mg/g using 0 V for ion loading and −1.5 V for regeneration of polyelectrolyte-activated carbon composite electrodes. These are made with a water soluble styrene butadiene rubber binder and positively (poly(diallyldimethyl-ammoniumchloride)) and negatively charged (polystyrene sulfonate) polyelectrolytes and used in combination with ion exchange membranes. This leads to increased separation performance, and exergy efficiency, whereas cumulative exergy loss values remain low, indicating promising resource use efficiencies, competitive with conventional membrane capacitive deionization (MCDI).

Carbodiimide-mediated immobilization of acidic biomolecules on reversed-charge zwitterionic sensor chip surfaces.

The carbodiimide-mediated amine coupling of protein ligands to sensor chips coated with anionic polycarboxylate hydrogels, such as carboxymethyl dextran, is the predominant covalent immobilization procedure utilized in optical biosensors, namely surface plasmon resonance (SPR) biosensors. Usually, electrostatic interactions at a slightly acidic pH and low ionic strength are employed to efficiently accumulate neutral and basic ligands on the chip surface, which are then covalently coupled by surface-bound active N-hydroxysuccinimide (NHS) esters. Unfortunately, this approach is not suitable for acidic proteins or other ligands with low isoelectric points (IEPs), such as nucleic acids, because the charge density of the polycarboxylates is greatly reduced at acidic pH or because electrostatic attraction cannot be achieved. To overcome these drawbacks, we have established a charge-reversal approach that allows the preconcentration of acidic proteins above their IEPs. A precisely controlled amount of tertiary amines is applied to reverse the previous anionic surface charge while maintaining carbodiimide compatibility with future protein immobilization. The mechanism of this reversed-charge immobilization approach was demonstrated employing protein A as a model protein and using attenuated total reflectance Fourier transform infrared spectroscopy, dynamic contact angle measurements, colorimetric quantification, and SPR analysis to characterize surface derivatization. Furthermore, even though it had previously proven impossible to preconcentrate DNA electrostatically and to covalently couple it to polyanionic chip surfaces, we demonstrated that our approach allowed DNA to be preconcentrated and immobilized in good yields. Graphical abstract Principle of the covalent immobilization of acidic ligands on reversed-charge zwitterionic sensor chip surfaces.

Magnetic Nanoparticles Interact and Pass an In Vitro Co-Culture Blood-Placenta Barrier Model.

Magnetic nanoparticles are interesting tools for biomedicine. Before application, critical prerequisites have to be fulfilled. An important issue is the contact and interaction with biological barriers such as the blood-placenta barrier. In order to study these processes in detail, suitable in vitro models are needed. For that purpose a blood-placenta barrier model based on the trophoblast-like cell line BeWo and primary placenta-derived pericytes was established. This model was characterized by molecular permeability, transepithelial electrical resistance and cell-cell-contact markers. Superparamagnetic iron oxide nanoparticles (SPIONs) with cationic, anionic or neutral surface charge were applied. The localization of the nanoparticles within the cells was illustrated by histochemistry. The time-dependent passage of the nanoparticles through the BeWo/pericyte barrier was measured by magnetic particle spectroscopy and atomic absorption spectroscopy. Cationically coated SPIONs exhibited the most extensive interaction with the BeWo cells and remained primarily in the BeWo/pericyte cell layer. In contrast, SPIONs with neutral and anionic surface charge were able to pass the cell layer to a higher extent and could be detected beyond the barrier after 24 h. This study showed that the mode of SPION interaction with and passage through the in vitro blood-placenta barrier model depends on the surface charge and the duration of treatment.

Morphological Analysis of Trafficking and Processing of Anionic and Cationic Liposomes in Cultured Cells.

Liposomes, artificial phospholipid vesicles, have been developed as a non-viral drug delivery system to allow contained agents to be efficiently delivered to target sites via systemic circulation. Liposomes have been used as a gene transfer tool with cultured cells; however, their precise trafficking and processing remain uncertain. Furthermore, liposomes with different surface charges are known to exhibit distinct properties. The purpose of the current study was to elucidate the intracellular trafficking and processing of liposomes with anionic and cationic surface charges from a morphological view point. We found that cationic liposomes (CLs) were more effectively taken by the cells than anionic liposomes (ALs). Confocal laser scanning microscopy and transmission electron microscopy demonstrated distinct intracellular localization and processing patterns of ALs and CLs. ALs and their contents were localized in lysosomes but not in cytosol, indicating that ALs are subjected to the endosome-lysosome system. In contrast, contents of CLs were distributed mainly in the cytosol. CLs appear to disturb the cell membrane and then collapse to release their contents into the cytosol. It is feasible that the contents of CLs enter the cytosol directly rather than via the endosome-lysosome system.

Impact of the surface charge of polydiacetylene micelles on their interaction with human innate immune protein C1q and the complement system

Polydiacetylene (pDA) micelles have been demonstrated to be effective drug carriers for cancer therapy in mouse model. However, little is known about their interaction with the human complement system, which constitutes an important part of the innate immune system and can cause severe hypersensitivity reactions. Herein, we investigate the influence of micelle surface charge on the binding of complement protein C1q, the target recognition unit that activates the classical complement pathway and performs a range of other important physiological functions. Besides the classical pathway, we also investigate the surface charge effect on complement activities through the other activation pathways, namely, the MBL-dependent lectin pathway and the alternative pathway. We synthesized three samples of pDA micelles bearing neutral, anionic, and cationic surface charge motifs, respectively. Surface plasmon resonance showed that none of these micelles interacted with C1q. Results from serum complement activation assays indicated that all micelles were inert to complement, except for the anionic pDA micelles, which activated the alternative pathway.

Influence of structural and surface properties of whey-derived peptides on zinc-chelating capacity, and in vitro gastric stability and bioaccessibility of the zinc-peptide complexes

Gastrointestinal stability of zinc-peptide complexes is essential for zinc delivery. As peptide surface charge can influence their metal complex stability, we evaluated the zinc-chelating capacity and stability of zinc complexes of whey protein hydrolysates (WPH), produced with Everlase (WPH-Ever; ζ-potential, −39mV) and papain (WPH-Pap; ζ-potential, −7mV), during simulated digestion. WPH-Ever had lower amount of zinc-binding amino acids but showed higher zinc-chelating capacity than WPH-Pap. This is attributable to the highly anionic surface charge of WPH-Ever for electrostatic interaction with zinc. Release of zinc during peptic digestion was lower for WPH-Ever-zinc, and over 50% of zinc remained bound in both peptide complexes after peptic-pancreatic digestion. Fourier transform infrared spectroscopy suggests the involvement of carboxylate ion, and sidechain carbon–oxygen of aspartate/glutamate and serine/threonine in zinc-peptide complexation. The findings indicate that strong zinc chelation can promote gastric stability and impede intestinal release, for peptides intended for use as dietary zinc carriers.

Zeta potential: a case study of cationic, anionic, and neutral liposomes.

Zeta potential is often used to approximate a nanoparticle's surface charge, i.e., cationic, anionic, or neutral character, and has become a standard characterization technique to evaluate nanoparticle surfaces. While useful, zeta potential values provide only very general conclusions about surface charge character. Without a thorough understanding of the measurement parameters and limitations of the technique, these values can become meaningless. This case study attempts to explore the sensitivity of zeta potential measurement using specifically formulated cationic, anionic, and neutral liposomes. This study examines zeta potential dependence on pH and ionic strength, resolving power, and highlights the sensitivity of zeta potential to charged liposomes. Liposomes were prepared with cholesterol, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), and varying amounts of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS). A strong linear relationship was noted between zeta potential values and the mole percentage of charged lipids within a liposome (e.g., cationic DOTAP or anionic DOPS). This finding could be used to formulate similar liposomes to a specific zeta potential, potentially of importance for systems sensitive to highly charged species. In addition, cationic and anionic liposomes were titrated with up to two mole percent of the neutral lipid 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (lipid-PEG; LP). Very small amounts of the lipid-PEG (<0.2mol%) were found to impart stability to the DOTAP- and DOPS-containing liposomes without significantly affecting other physicochemical properties of the formulation, providing a simple approach to making stable liposomes with cationic and anionic surface charge.

Mechanically ground softwood fines as a raw material for cellulosic applications

Utilization of mechanically manufactured lignocellulosic fines (LCNFs) was investigated in making filaments and films. The LCNFs particles were prepared by using a mechanical grinding method with a w-profile grinding stone that produces mostly fines with dimensions in the micrometer scale. The chemical and elemental composition of the w-stone ground LCNFs particles was investigated. It was found that the mechanically manufactured material exhibited the chemical structure of native wood. The LCNFs particles had an anionic surface charge making them colloidally semi-stable in water. The short length of the fines particles prevents their effective mechanical entanglement, which sets some limitations on preparation of filaments and films. Filament manufacturing required the use of a composite approach with carboxymethyl cellulose (CMC) as a binder polymer. The filament was manufactured by using dry-jet wet spinning with aluminium sulfate crosslinking. The chemical composition, crosslinking mechanism, and mechanical properties of the composite filaments were investigated. The composite approach with CMC was also used to prepare composite films with good mechanical performance. The investigated LCNFs material could be utilized in all-lignocomposite applications with cellulose derivatives, where biodegradability and biobased characteristics are desired properties.

Functionalized Triblock Copolymer Vectors for the Treatment of Acute Lymphoblastic Leukemia.

The chemotherapeutic Parthenolide is an exciting new candidate for the treatment of acute lymphoblastic leukemia, but like many other small-molecule drugs, it has low aqueous solubility. As a consequence, Parthenolide can only be administered clinically in the presence of harmful cosolvents. Accordingly, we describe the synthesis, characterization, and testing of a range of biocompatible triblock copolymer micelles as particle-based delivery vectors for the hydrophobic drug Parthenolide. The drug-loaded particles are produced via an emulsion-to-micelle transition method, and the effects of introducing anionic and cationic surface charges on stability, drug sequestration, biocompatibility, and efficacy are investigated. Significantly, we demonstrate high levels of efficacy in the organic solvent-free systems against human mesenchymal stem cells and primary T-acute lymphoblastic leukemia patient cells, highlighting the effectiveness of the delivery vectors for the treatment of acute lymphoblastic leukemia.

Electrostatic layer-by-layer construction of fibrous TMV biofilms.

As nature's choice in designing complex architectures, the bottom-up assembly of nanoscale building blocks offers unique solutions in achieving more complex and smaller morphologies with wide-ranging applications in medicine, energy, and materials science as compared to top-down manufacturing. In this work, we employ charged tobacco mosaic virus (TMV-wt and TMV-lys) nanoparticles in constructing multilayered fibrous networks via electrostatic layer-by-layer (LbL) deposition. In neutral aqueous media, TMV-wt assumes an anionic surface charge. TMV-wt was paired with a genetically engineered TMV-lys variant that displays a corona of lysine side chains on its solvent-exposed surface. The electrostatic interaction between TMV-wt and TMV-lys nanoparticles became the driving force in the highly controlled buildup of the multilayer TMV constructs. Since the resulting morphology closely resembles the 3-dimensional fibrous network of an extracellular matrix (ECM), the capability of the TMV assemblies to support the adhesion of NIH-3T3 fibroblast cells was investigated, demonstrating potential utility in regenerative medicine. Lastly, the layer-by-layer deposition was extended to release the TMV scaffolds as free-standing biomembranes. To demonstrate potential application in drug delivery or vaccine technology, cargo-functionalized TMV biofilms were programmed.