Programmed polymersomes with spatio-temporal delivery of antigen and dual-adjuvants for efficient dendritic cells-based cancer immunotherapy

Since antigen and adjuvant are rapid clearance in vivo, insufficient delivery to induce dendritic cells (DCs) maturation and cross-presentation, as well as limited migration efficiency of DCs to secondary lymph organs, greatly hinders the development of DCs-based immunotherapy. Herein, PCL-PEG-PCL polymersomes (PCEP-PS) as antigen and adjuvants delivery nanoplatforms (IMO-PS) were well-designed, which can electrostatically adsorb OVA antigen on the surface via DOTAP lipid and effectively encapsulate OVA antigen into the inner hydrophilic cavity to achieve both initial antigen exposure as well as slow and sustained antigen release, incorporate MPLA within the lipid layer to ligate with extracellular TLR4 of DCs as well as encapsulate IMQ in the hydrophobic membrane to ligate with intracellular TLR7/8 of DCs for activating synergistic immune responses via different signaling pathways. The IMO-PS significantly improved antigen uptake, promoted DCs maturation and cytokines production. DCs treated with IMO-PS could enhance migration into draining lymphoid nodes, and eventually induced antigen-specific CD8⁺ and CD4⁺ T cell responses and OVA-specific cytotoxic T lymphocyte (CTL) responses. Prophylactic vaccination of EG7-OVA tumor-bearing mice by IMO-PS + DCs significantly extended tumor-free time, effectively suppressed tumor growth, and greatly extended median survival time. The strategy may provide an effective nanoplatform for co-delivery antigen and dual-adjuvants in a spatio-temporally programmed manner for DC-based cancer immunotherapy.     

HPMA‐Based Nanocarriers for Effective Immune System Stimulation

The selective activation of the immune system using nanoparticles as a drug delivery system is a promising field in cancer therapy. Block copolymers from HPMA and laurylmethacrylate‐co‐hymecromone‐methacrylate allow the preparation of multifunctionalized core‐crosslinked micelles of variable size. To activate dendritic cells (DCs) as antigen presenting cells, the carbohydrates mannose and trimannose are introduced into the hydrophilic corona as DC targeting units. To activate DCs, a lipophilic adjuvant (L18‐MDP) is incorporated into the core of the micelles. To elicit an immune response, a model antigen peptide (SIINFEKL) is attached to the polymeric nanoparticle—in addition—via a click reaction with the terminal azide. Thereafter, the differently functionalized micelles are chemically and biologically characterized. While the core‐crosslinked micelles without carbohydrate units are hardly bound by DCs, mannose and trimannose functionalization lead to a strong binding. Flow cytometric analysis and blocking studies employing mannan suggest the requirement of the mannose receptor and DC‐SIGN for effective micelle binding. It could be suppressed by blocking with mannan. Adjuvant‐loaded micelles functionalized with mannose and trimannose activate DCs, and DCs preincubated with antigen‐conjugated micelles induce proliferation of antigen‐specific CD8+ T cells.     

Mannose‐Modified Serum Exosomes for the Elevated Uptake to Murine Dendritic Cells and Lymphatic Accumulation

The surface of bovine serum‐derived exosomes (EXOs) are modified with α‐d ‐mannose for facile interaction with mannose receptors on dendritic cells (DCs) and for efficient delivery of immune stimulators to the DCs. The surface of the EXOs is modified with polyethylene glycol (PEG) without particle aggregation (≈50 nm) via the incorporation of 1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine (DSPE) into the lipid layer of the EXO, compared to chemical conjugation by N‐hydroxysuccinimide activated PEG (NHS‐PEG). PEG modification onto the exosomal surface significantly decreases the non‐specific cellular uptake of the EXOs into the DCs. However, the EXOs with mannose‐conjugated PEG‐DSPE (EXO‐PEG‐man) exhibit excellent intracellular uptake into the DCs and boost the immune response by the incorporation of adjuvant, monophosphoryl lipid A (MPLA) within the EXO. After an intradermal injection, a higher retention of EXO‐PEG‐man is observed in the lymph nodes, which could be used for the efficient delivery of immune stimulators and antigens to the lymph nodes in vivo.     

In situ ethylene copolymerization with an olefin-type monomer for one-pot synthesis of polyethylene tethered on multi-walled carbon nanotubes

A one-pot procedure for the synthesis of polyethylene tethered on multi-walled carbon nanotubes by in situ ethylene copolymerization with an olefin-type comonomer, α-alkene functionalized multi-walled carbon nanotubes (MW - CH = CH₂) is reported. The covalent linkage between polyethylene and multi-walled carbon nanotubes is demonstrated. The MWCNTs are chemically oxidized first by a strong oxidizing agent and then functionalized with chlorocarbonyl groups (MW-COCl) via reacting with thionyl chloride. The MW-CH=CH₂ are obtained by esterification of ω-undecylenyl alcohol with MW-COCl. The MW-CH=CH₂ may serve as olefin-type comonomers to further synthesize core-shell structured copolymers with a multi-walled carbon nanotubes core grafted with side chains of polyethylene via rac-(en)(THInd)₂ZrCl₂ copolymerization catalyst. The core-shell structured nanocomposites were characterized by means of ¹H-NMR, SEM, FTIR and TGA. The results confirmed the formation of polyethylene chains growing from the surface of multi-walled carbon nanotubes.     

Skin Constituents as Cosmetic Ingredients. Part III: A Molecular Modeling Study of Bio‐Mimetic Monoglycerides Behavior at the Squalene‐Water Interface

Tetrakis(4-hydroxylphenyl)porphyrin (THPP) modified multi-walled carbon nanotubes were synthesized. Meanwhile, THPP or tetrakis(4-hydroxylphenyl)porphyrin cobalt(II) (CoTHPP) was introduced on the surface of carboxyl-functionalized multi-walled carbon nanotubes (MWNTs-COOH) and amino-functionalized multi-walled carbon nanotubes (MWNTs-NH₂) to form a series of complexes, respectively. TEM images indicated that the assemblies were made of the short chipping carbon nanotubes and the long assembled carbon nanotubes. The UV-vis spectra and fluorescence spectra were used to investigate the properties of the porphyrins assembled on the carbon nanotubes.     

Effect of support on activity of palladium catalysts in nitrobenzene hydrogenation

The effect of two types of catalysts on the activity of the catalytic hydrogenation of nitrobenzene was studied. Catalysts were prepared by the surface deposition of palladium hydroxide with a simultaneous reduction with formaldehyde in a basic environment and were characterised by X-ray powder diffraction, transmission electron microscopy, adsorption-desorption, and catalytic tests — hydrogenation of nitrobenzene in methanol. The influence of the supports’ (activated carbon and a mixture of activated carbon and multi-walled carbon nanotubes) surface area is discussed. Despite having a size comparable (4–5 nm) to crystallites of metallic palladium, the catalyst prepared on a mixture of activated carbon and nanotubes (Pd/C/CNT) was significantly less active than the catalyst prepared on pure activated carbon (Pd/C); the rate of this reaction was approximately 30 % lower than the initial reaction rate. This feature could be attributed to the lower specific surface area of the Pd/C/CNT (531 m² g^?1) in comparison with the Pd/C (692 m² g^?1).     

Evaluation of carbon nanotubes as a solid-phase extraction adsorbent for the extraction of cephalosporins antibiotics, sulfonamides and phenolic compounds from aqueous solution

The adsorptive potential of carbon nanotubes (single-walled carbon nanotubes and multi-walled carbon nanotubes) for solid-phase extraction of three groups of highly polar compounds (namely cephalosporins antibiotics, sulfonamides and phenolic compounds) was tested in this article. The analytes were strongly retained by the carbon nanotubes. And acceptable recoveries were obtained with the addition of ammonium acetate into eluents. The effects of solution pH on the recoveries of the antibiotics and phenolic compounds were examined. To check the retention abilities of three groups of compounds on carbon nanotubes, fixed amount of each analyte was added to different volumes (up to 500 mL) of aqueous solution, and then extracted by the sorbents. Comparative studies showed that the carbon nanotubes were much superior to C₁₈ for the extraction of the highly polar analytes. For the cephalosporins antibiotics and sulfonamides, the carbon nanotubes showed stronger retention capability than graphitized carbon blacks, but for some of the phenolic compounds graphitized carbon blacks seemed to be more suitable, indicating different retention mechanisms of these analytes. To further assess the enrichment ability of carbon nanotubes for highly polar compounds, the solid-phase extraction method of multi-walled carbon nanotubes packed cartridge was well developed, and the sulfonamides were used as model compounds. Under the optimal procedures, the detection limits of sulfonamides were in the range of 27-38 ng L⁻¹. The spiked recoveries from several real water samples obtained for sulfathiazole and sulfadiazine ranged from 55% to 79% and 72% to 92%, respectively, while the recoveries of sulfapyridine and sulfamethazine were in the range of 85-102%.     

Efficient anchorage of Pt clusters on N-doped carbon nanotubes and their catalytic activity

We report an efficient method for anchoring Pt clusters (e.g., 6 nm in size) on the surfaces of N-doped multi-walled carbon nanotubes (MWNTs-CN_x) using a relatively simple method consisting of a hydrothermal treatment of Na₂[PtCl₆] · 6H₂O and N-doped nanotubes dispersed in acetic acid. The catalytic properties of this material were evaluated finding that the conversion of cinnamaldehyde using Pt-coated MWNTs-CN_x could increase up to 6 times with respect to that obtained for uncoated MWNTs-CN_x and pure carbon CNTs. Therefore, we envisage this material could be either used as an efficient catalyst or as a sensor.     

Voltammetric determination of bisphenol A in food package by a glassy carbon electrode modified with carboxylated multi-walled carbon nanotubes

A highly sensitive and mercury-free method for determination of bisphenol A (BPA) was established using a glassy carbon electrode that was modified with carboxylated multi-walled carbon nanotubes. A sensitive oxidation peak is found at 550?mV in linear sweep voltammograms at pH?7. Based on this finding, trace levels of bisphenol A can be determined over a concentration range that is linear from 10?nM to 10⁴?nM, the correlation coefficient being 0.9983, and the detection limit (S/N?=?3) being 5.0?nM. The method was successfully applied to the determination of BPA in food package.

Facile synthesis of magnetic silica-mannan nanocomposites for enhancement in internalization and immune response of dendritic cells

Superparamagnetic iron oxide nanoparticles (SPIONs) have been extensively exploited in biomedicine, especially as contrasting agents. In this work, SPIONs are of our interest as directing agents to the targeted dendritic cells (DCs). Mannan extracted from Saccharomyces cerevisiae was used as DCs targeting moieties. Herein, nanocomposites of silica magnetic nanoparticle-mannan (S-SPION-MN) were successfully synthesized as a magnetically assisted delivery system. The materials before Silica magnetic nanoparticles (S-SPION) and after mannan modification were characterized using a vibrating sample magnetometer to confirm their superparamagnetic character. The change in zeta potential from highly negative charge to slightly negative charge of the composites suggested the successful attachment of mannan on their surface. Chemical analysis using x-ray photoelectron spectroscopy revealed the attachment of mannan through chemical bonding, corresponding to the observation of high stability of the particles over a two-week period. The synthesized materials were investigated for cytotoxicity, DC maturation, cytokine production, and cellular uptake. Moderate cell viability was observed after stimulating cells with the particulate mannan, S-SPION-MN, due to high activation of DCs. Under a magnetic induction, S-SPION-MN showed significant enhancement of DCs targeting within 15 min. Owing to the incorporation of mannan and SPIONs, the S-SPION-MN greatly enhanced cellular uptake and accordingly resulted in high DC activation and maturation. The resulted nanocomposites can be beneficial as a potential candidate in antigen delivery to targeted immune cells for further in vivo study.     

Fullerenes inside carbon nanotubes and multi-walled carbon nanotubes: optimum and maximum sizes

The potential energies of interaction between carbon nanotubes and internal fullerenes of spherical and ellipsoidal shape, as well as between nanotubes in multi-walled nanotubes were calculated using the Lennard–Jones (LJ) potential for carbon–carbon interactions. The optimum and maximum size of internal fullerenes and multi-walled nanotubes are determined as a function of the external nanotube radius. It was found that at the potential energy minimum, the van der Waals distance is close to that in graphite for all studied cases. The calculated results agree with available experimental observations and could be used as a guide for future experiments.     

Electron-transfer properties of different carbon nanotube materials,and their use in glucose biosensors

Different types of carbon nanotube material (single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs) of different internal diameter) have been used for preparation of CNT-modified glassy-carbon electrodes. Redox reactions involving ferricyanide and hydrogen peroxide were examined at the CNT-modified electrodes. Electrodes modified with SWCNTs usually had better electron-transfer properties than MWCNT-modified electrodes. Glucose biosensors were also prepared with electropolymerized polyphenylenediamine films, CNT materials, and glucose oxidase. Amperometric behavior in glucose determination was examined. SWCNT-modified glucose biosensors usually had a wider dynamic range (from 0.1 to 5.5 mmol L⁻¹) and greater sensitivity in glucose determination. The detection limit was estimated to be 0.05 mmol L⁻¹.     

Highly sensitive detection of silybin based on adsorptive stripping analysis at single-sided heated screen-printed carbon electrodes modified with multi-walled carbon nanotubes with direct current heating

A new disposable multi-walled carbon nanotubes modified single-sided heated screen-printed carbon electrode (MWNT/ss-HSPCE) was fabricated. The electrochemical behavior of silybin was investigated by cyclic voltammetry and the probable electrode reaction mechanism was proposed. A simple and cheap direct current heating supplier was used to heating the electrode for adsorptive accumulation of silybin. The square wave voltammetric stripping peak current of silybin at MWNT/ss-HSPCE with an elevated electrode temperature of 50 °C only during accumulation step was dramatically improved compared with that at bare single-sided heated screen-printed carbon electrode (ss-HSPCE) without heating. This enhancement was mainly contributed to the combination of the advantages of multi-walled carbon nanotubes and electrically heated electrodes. Under optimum conditions, two detection linear ranges of silybin were from 1.0 × 10⁻⁹ to 1.0 × 10⁻⁷ M and 3.0 × 10⁻⁷ to 1.0 × 10⁻⁶ M. A detection limit of 5.0 × 10⁻¹⁰ M could be obtained (S/N = 3), which was more than two magnitudes lower than that at bare ss-HSPCE without heating. To the best of our knowledge, this was also at least two magnitudes lower than any others for electrochemical detection of silybin in the literature. Finally, the method was successfully applied to the determination of silybin in pharmaceutical tablets.     

Porous carbon nanotubes improved sulfur composite cathode for lithium-sulfur battery

Porous multi-walled carbon nanotubes (PCNTs) with multiple mesopores structure are synthesized through activation of multi-walled carbon nanotubes (MWCNTs) by potassium hydroxide. The potassium hydroxide activation process results in a significantly enhanced specific surface area with numerous small pores. The as-obtained PCNTs are employed as the conductive matrix for sulfur in the sulfur cathode. Compared with the composite sulfur cathode based on the original MWCNTs, the sulfur-PCNTs cathode shows a significantly improved cycle performance and columbic efficiency. The reversible capacity is 530 mAh?g^?1 and columbic efficiency is 90 % after 100 cycles at a current density of 100 mA?g^?1. The improvement in the electrochemical performance for S-PCNT is mainly attributed to the enlarged surface area and the porous structure of the unique mesopores carbon nanotube host, which cannot only facilitate transport of electrons and Li⁺ ions, but also trap polysulfides, retard the shuttle effect during charge/discharge process.     

Coating Multi-walled Carbon Nanotubes with Uniform Silica Shells:Independent of Surface Chemistry

A facile and general method was described to coat six types of multi-walled carbon nanotubes, functionalized by either noncovalent or covalent way, with smooth silica shells. 3-Aminopropyltriethoxysilane(APTES) and pH value play important roles in the coating process and the thickness of silica shell could be controlled by the added amount of silicon alkoxides. After the removal of multi-walled carbon nanotubes by calcination, the silica nanotubes were successfully prepared.     

Magnetic assembled electrochemical platform using Fe2O3 filled carbon nanotubes and enzyme

A novel electrochemical nanostructured biosensor based on carbon nanotubes (CNTs) has been constructed by magnetic assembly method. The magnetic multi-walled carbon nanotubes (M-MWNTs) were prepared by introducing Fe₂O₃ nanoparticles into the nanotubes. Thus the multilayered functional platform could be assembled with the aid of magnetic field. The horseradish peroxidase (HRP) was employed as a model enzyme to demonstrate the final performance of the nanostructured biosensor. SEM, UV–vis spectroscopy and electrochemical techniques were used for characterization of assembly process. The resulting three-dimensional M-MWNTs/HRP multilayer films have showed satisfactory stability, biocompatibility and electrochemical properties.     

Multi-walled carbon nanotubes used as support for lipase from <Emphasis Type="Italic">Burkholderia cepacia</Emphasis>

Commercial lipase from Burkholderia cepacia is immobilized on functionalized multi-walled carbon nanotubes (MWNT-COOH and MWNT-OH) provided by a physical adsorption. The immobilization processes for the carbon nanotubes are defined using immobilization time (0–30 min) and distinct adsorbent:adsorbate ratios (1:4, 1:7, and 1:10) with lipase loading of 100, 175, and 250 mg, respectively. The characterization of the immobilized preparations, the free lipase, and the pure nanotubes (MWNT-COOH and MWNT-OH) indicate that the lipase adsorption is increased. Thermogravimetric analysis, differential scanning calorimetry, and scanning electron microscopy are used. The specific surface area, pore volumes, and average pore diameters are determined by nitrogen adsorption–desorption isotherms. For the pure lipase, in the range between 40 and 300 °C, the micrograph is acquired. Experimental results clearly show an effective lipase adsorption in a lower period of time (5 min) in MWNT-COOH and MWNT-OH as well as a decrease in the surface area (98.30–45.9(86)?±?2.5 and 97.61–37.71?±?3.3(7) m² g^?1) and the pore volume (0.48–0.25?±?0.01 and 0.39–0.24?±?0.05 cm³ g^?1), indicating that functionalized multi-walled carbon nanotubes can be successfully used as enzyme support.     

In situ PEI and formic acid directed formation of Pt NPs/MWNTs hybrid material with excellent electrocatalytic activity

A hybrid material based on Pt nanoparticles (Pt NPs) and multi-walled carbon nanotubes (MWNTs) was fabricated with the assistance of PEI and formic acid. The cationic polyelectrolyte PEI not only favored the homogenous dispersion of carbon nanotubes (CNTs) in water, but also provided sites for the adsorption of anionic ions PtCl₄²⁻ on the MWNTs’ sidewalls. Deposition of Pt NPs on the MWNTs’ sidewalls was realized by in situ chemical reduction of anionic ions PtCl₄²⁻ with formic acid. The hybrid material was characterized with TEM, XRD and XPS. Its excellent electrocatalytic activity towards both oxygen reduction in acid media and dopamine redox was also discussed.     

Electrochemical DNA biosensors based on platinum nanoparticles combined carbon nanotubes

Platinum nanoparticles were used in combination with multi-walled carbon nanotubes (MWCNTs) for fabricating sensitivity-enhanced electrochemical DNA biosensor. Multi-walled carbon nanotubes and platinum nanoparticles were dispersed in Nafion, which were used to fabricate the modification of the glassy carbon electrode (GCE) surface. Oligonucleotides with amino groups at the 5′ end were covalently linked onto carboxylic groups of MWCNTs on the electrode. The hybridization events were monitored by differential pulse voltammetry (DPV) measurement of the intercalated daunomycin. Due to the ability of carbon nanotubes to promote electron-transfer reactions, the high catalytic activities of platinum nanoparticles for chemical reactions, the sensitivity of presented electrochemical DNA biosensors was remarkably improved. The detection limit of the method for target DNA was 1.0 × 10⁻¹¹ mol l⁻¹.     

Electrochemical behavior and determination of fluphenazine at multi-walled carbon nanotubes/(3-mercaptopropyl)trimethoxysilane bilayer modified gold electrodes

A novel multi-walled carbon nanotubes/(3-mercaptopropyl)trimethoxysilane (MPS) bilayer modified gold electrode was prepared and used to study the electrochemcial behavior of fluphenazine and determine it. Fluphenazine could effectively accumulate at this electrode and produce two anodic peaks at about 0.78 V and 0.93 V (versus SCE). The peak at about 0.78 V was much higher and sensitive, thus it could be applied to the determination. Various conditions were optimized for practical application. Under the selected conditions (i.e. 0.05 M pH 3.5 HCOOH-HCOONa buffer solution, 5 μl 1 mg ml⁻¹ multi-walled carbon nanotubes for Φ=2.0 mm electrode, accumulation at open circuit for 180 s), the anodic peak current was linear to fluphenazine concentration in the range from 5×10⁻⁸ to 1.5×10⁻⁵ M with correlation coefficient of 0.9984, the detection limit was 1×10⁻⁸ M. For a 1×10⁻⁵ M fluphenazine solution, the relative standard deviation of peak current was 2.51% (n=8). This method was successfully applied to the determination of fluphenazine in drug samples and the recovery was 96.4-104.4%. The electrode could be easily regenerated and exhibited some selectivity, but some surfactants reduced the peak current greatly. The modified electrode was characterized by alternating current impedance and electrochemical probe.