Recently, drug-controlled release nanotechnology has gained special attention in biomedicine. This work focuses on developing novel electrospun polymeric nanofibers (NFs) for buccal delivery of VEN to avoid the hepatic metabolism and enzymatic degradation in the GIT and develop an effective control of drug release. The optimized NFs were obtained by blending polylactic acid (PLA), and poly (ɛ-caprolactone) (PCL) fixed at a ratio of 1:1. It was characterized for morphology, drug-loading, FTIR, XRD, DSC, and in vitro drug release. Ex vivo permeability of the blend NFs was assessed using chicken pouch mucosa compared to VEN suspension, followed by histopathological examination. Further, the cytotoxic effect in three different cell lines using WST-1 assay. SEM morphologies refer to defect-free uniform NFs of PLA, PCL, and PLA/PCL mats. These fibers had a diameter ranging from 200 to 500 nm. The physico-thermal characterization of NFs depicted that the drug was successfully loaded and in an amorphous state in the PLA/PCL NFs. In vitro release of NFs substantiated a bi-phasic profile with an initial burst release of about 30% in the initial 0.5 h and a prolonged cumulative release pattern that reached 80% over 96 h following a non-Fickian diffusion mechanism. Ex vivo permeation emphasizes the major enhancement of the sustained drug release and the noticeable decrease in the permeability of the drug from NFs. Cytotoxicity data found that IC50 of VEN alone was 217.55 μg/mL, then VEN-NFs recorded an IC50 value of 250.62 μg/mL, and plain NFs showed the lowest toxicity and IC50 440.48 μg/mL in oral epithelial cells (OEC). Histopathology and cell toxicity studies demonstrated the preserved mucosal architecture and the preclinical safety. The developed PLA/PCL NFs can be promising drug carriers to introduce a step-change in improved psychiatric treatment healthcare.

Lactobacillus delbrueckii JCM 1002T grows on highly polymerized inulin-type fructans as its sole carbon source. When it was grown on inulin, a > 10 kb long gene cluster inuABCDEF (Ldb1381-1386) encoding a plausible ABC transporter was suggested to be induced, since a transcriptome analysis revealed that the fourth gene inuD (Ldb1384) was up-regulated most prominently. Although Bacillus subtilis 168 is originally unable to utilize inulin, it became to grow on inulin upon heterologous expression of inuABCDEF. When freshly cultured cells of the recombinant B. subtilis were then densely suspended in buffer containing inulin polymers and incubated, inulin gradually disappeared from the buffer and accumulated in the cells without being degraded, whereas levan-type fructans did not disappear. The results imply that inuABCDEF might encode a novel ABC transporter in L. delbrueckii to "monopolize" inulin polymers selectively, thereby, providing a possible advantage in competition with other concomitant inulin-utilizing bacteria.

Single Cell Force Spectroscopy was combined with Electrochemical-AFM to quantify the adhesion between live single cells and conducting polymers whilst simultaneously applying a voltage to electrically switch the polymer from oxidized to reduced states. The cell-conducting polymer adhesion represents the non-specific interaction between cell surface glycocalyx molecules and polymer groups such as sulfonate and dodecylbenzene groups, which rearrange their orientation during electrical switching. Single cell adhesion significantly increases as the polymer is switched from an oxidized to fully reduced state, indicating stronger cell binding to sulfonate groups as opposed to hydrophobic groups. This increase in single cell adhesion is concomitant with an increase in surface hydrophilicity and uptake of cell media, driven by cation movement, into the polymer film during electrochemical reduction. Binding forces between the glycocalyx and polymer surface are indicative of molecular-level interactions and during electrical stimulation there is a decrease in both the binding force and stiffness of the adhesive bonds. The study provides insight into the effects of electrochemical switching on cell adhesion at the cell-conducting polymer interface and is more broadly applicable to elucidating the binding of cell adhesion molecules in the presence of electrical fields and directly at electrode interfaces.

Selective and rapid regulation of ionic channels is pivotal to the understanding of physiological processes and has a crucial impact in developing novel therapeutic strategies. Transient Receptor Potential (TRP) channels are emerging as essential cellular switches that allow animals to respond to their environment. In particular, the Vanilloid Receptor 1 (TRPV1), besides being involved in the body temperature regulation and in the response to pain, has important roles in several neuronal functions, as cytoskeleton dynamics, injured neurons regeneration, synaptic plasticity. Currently available tools to modulate TRPV1 activity suffer from limited spatial selectivity, do not allow for temporally precise control, and are usually not reversible, thus limiting their application potential. The use of optical excitation would allow for overcoming all these limitations. Here, we propose a novel strategy, based on the use of light-sensitive, conjugated polymers. We demonstrate that illumination of a polymer thin film leads to reliable, robust and temporally precise control of TRPV1 channels. Interestingly, the activation of the channel is due to the combination of two different, locally confined effects, namely the release of thermal energy from the polymer surface and the variation of the local ionic concentration at the cell/polymer interface, both mediated by the polymer photoexcitation.

Absolute molecular weight values obtained by gel permeation chromatography with multi angle light scattering of PEDOTF8 were approximately 65% of the relative molecular weight values obtained by gel permeation chromatography using polystyrene standards. Both light absorption and molecular weight measurements showed the effective conjugation lengths (absolute molecular weight <2600, relative molecular weight <4000, number of EDOT-F8 units: n < ca. 5 unit). The low molecular weight polymers showed higher energy absorption and fluorescence bands. Molecular weight also affected the electrochemical process of the polymer films. The high molecular weight PEDOTF8 (number average molecular weight >70000) showed a higher redox stability than the low molecular weight one. The two polymers with number average molecular weights of 70200 and 40000 retained 65% and 25% of the charge storage capacity after 100 electrochemical scans, respectively. Square-wave potential step absorptiometry measurements of the polymers with number average molecular weights of 70200 and 40000 showed that the optical contrasts remain stable after ca. 55 and three cycles, respectively. The high molecular weight polymer has a high electrochemical stability and would be a good material for optoelectronic devices.

Increased glutamine uptake toward the elevated glutaminolysis is one of the hallmarks of tumour cells. This aberrant glutamine metabolism has recently attracted considerable attention as a diagnostic and therapeutic target. Herein, we developed glutamine-functionalized polymer to achieve a selective high affinity to tumour cells overexpressing glutaminolysis-related transporter ASCT2. In in vitro study, our developed polymer exhibited faster and higher cellular uptake in tumour cells than that in normal cells. Uptake inhibition study revealed the dominant contribution of ASCT2 to the polymer-cell interaction. Furthermore, the binding affinity of the polymer to tumour cells was estimated to be comparable to that of the potent ligand molecules reported in the literature. In in vivo study, the polymer showed prolonged retention at tumour site after intratumoral injection. This study offers a novel approach for designing tumour cell-binding synthetic polymers through the recognition of dense transporters related to tumour-associated metabolism.

Recently developed sub-resonance tapping modes (such as Digital Pulse, Peak Force Tapping, HybriD, etc.) of atomic force microscopy (AFM) allow imaging of compositional contrast of (bio)materials and biological cells down to the nanoscale. Here we report on a powerful extension of those modes, "ringing" mode, which more than doubles the number of non-trivial physical channels that can be collected with a regular sub-resonance tapping. It can simultaneously record five new additional compositional parameters related to adhesive and viscoelastic properties of the sample surface: the restored (averaged) adhesion, adhesion height, pull-off neck height, detachment distance, and detachment energy losses. Ringing mode can be up to 20 times faster and showing fewer artifacts compared to the existing sub-resonance tapping modes. Ringing mode is based on an analysis of ringing signal of the AFM cantilever after detaching the AFM probe from the sample surface (this signal is currently treated as noise, and typically filtered out in the existing modes). We demonstrate that this new mode allows recording robust and unique information on fixed human epithelial cells, corneocyte skin flakes, and polymers used for bioimplants.

In recent years, several nanocarrier synthesis methods have been developed. In cancer therapy, the use of smart nanocarriers is of interest. Smart nanocarriers respond to their environment and can release their cargo in a controlled manner under the action of internal or external stimuli. In this work, we report on the development of an aerosol-assisted method for the synthesis of curcumin-loaded chitosan/alginate-based polymeric nanocarrier (CurNCs). A custom-fabricated multi-nebulizer system was utilized for the synthesis of CurNCs. The developed system comprises three main parts a sprayer, an electric heater tunnel, and a collector. Curcumin and chitosan solutions were sprayed using a pneumatic multinebulizer into the electric heater tunnel to form chitosan-curcumin assemblies. Then, the aerosol was guided into the collector solution containing sodium alginate and tri-poly phosphate aqueous solution for further cross-linkage. The synthesized CurNCs were characterized using TEM, DLS, and FTIR techniques. The TEM size of the nanoparticles was 8.62 ± 2.25 nm. The release experiments revealed that the nanocarrier is sensitive to the environment pH as more curcumin is released at acidic pH values (as is the case for cancerous tissues) compared to physiological pH. The curcumin content of the nanocarrier was 77.27 mg g-1 with a drug loading efficiency of 62%. The in-vitro cytotoxicity of the synthesized nanocarrier was evaluated against the MCF7 breast cancer cell line. The IC50 concentrations for CurNCs and curcumin were obtained as 14.86 and 16.45 mg mL-1, respectively. The results showed that while the empty nanocarrier shows non-significant cytotoxicity, the CurNCs impact the cell culture and cause prolonged cell deaths. Overall, pH-responsive curcumin polymeric nanocarrier was synthesized using a custom fabricated aerosol-based method. The method enabled fast and feasible synthesis of the nanocarrier with high efficiency.

Non-covalent polymers have remarkable advantages over synthetic polymers for wide biomedical applications. In this study, non-covalent polymers from self-assembled boric acid were used as the capping reagent to replace synthetic polymers in drug crystallization. Under acidic pH, boric acid self-assembled on the surface of drug nanocrystals to form polymers with network-like structures held together by hydrogen bonds. Coating driven by boric acid self-assembly had negligible effects on drug crystallinity and structure but resulted in drug nanocrystals with excellent dispersion properties that aided in the formation of a more stable suspension. Boric acid coating improved drug stability dramatically by preventing drug molecules from undergoing water hydrolysis in a neutral environment. More importantly, the specific reactivity of orthoboric groups to diols in cell glycocalyx facilitated a rapid cross-membrane translocation of drug nanocrystals, leading to efficient intracellular drug delivery, especially on cancer cells with highly expressed sialic acids. Boric acid coated nanocrystals of camptothecin, an anticancer drug with poor aqueous solubility and stability, demonstrated extreme cytotoxic activity (IC50 < 5.0 μg/mL) to cancer cells compared to synthetic polymer coated CPT nanocrystals and free CPT. Surface coating using non-covalent polymers from self-assembled boric acid will have wide biomedical applications especially in biomaterials and drug delivery field.

Aerobic granular sludge (AGS) is a proven resource for the recovery of biopolymers like alginate-like polymers (ALP). This is the first report on the dynamics of ALP produced by AGS (ALP-AGS) in a full-scale wastewater treatment plant (WWTP), optimization of ALP recovery from AGS, and adsorption of cadmium (Cd2+) by ALP. Recovery of ALP was highest when using 120 mL of 0.2 M Na2CO3 at 70 °C for 45 min. Seasonal (1.5 years, over 3100 cycles) and intra-cycle changes in ALP-AGS in the WWTP were monitored. The ALP content in AGS increased in the transition period between winter and spring, reaching over 150 mg/g MLSS. In the batch reactor cycle, the ALP-AGS level peaked 2 h after the start of aeration (mean peak level: 120 mg/g MLSS), then decreased about two-fold by the end of the cycle. The ALP-AGS had a small surface area and a lamellar structure with crystalline outgrowths. The optimal conditions of Cd2+ adsorption with ALP were a dosage of 7.9 g d.m./L, a pH of 4-8, and an equilibrium time of 60 min. Carboxyl and hydroxyl groups were the key functional groups involved in Cd2+ adsorption. According to the Sips model, the maximum Cd2+ adsorption capacity of ALP-AGS was 29.5 mg/g d.m., which is similar to that of commercial alginate. AGS is a richer source of ALP than activated sludge, which ensures the cost-effectiveness of ALP recovery and increases the sustainability of wastewater treatment. Information on the chemical properties and yields of ALP from full-scale WWTPs is important for downstream applications with the recovered ALP.

Redox targeting reaction is an emerging idea for boosting the energy density of redox-flow batteries: mobile redox mediators transport electrical charges in the cells, whereas large-density electrode-active materials are fixed in tanks. This study reports 4 V-class organic polymer mediators using thianthrene derivatives as redox units. The higher potentials than conventional organic mediators (up to 3.8 V) enable charging LiMn2O4 as an inorganic cathode offering a large theoretical volumetric capacity of 500 Ah/L. Soluble or nanoparticle polymer design is beneficial for suppressing crossover reactions (ca. 3% after 300 h), simultaneously contributing to mediation reactions. The successful mediation cycles observed by repeated charging/discharging steps indicate the future capability of designing particle-based redox targeting systems with porous separators, benefiting from higher energy density and lower cost.

Strategic delivery of IRDye 700DX (photosensitizer) is a key for improving its effect in photodynamic therapy. In this study, we have synthesized IRDye 700DX-conjugated polymers containing multiple cyclic RGD peptides to deliver IRDye 700DX selectively to tumor cells and tumor-associated blood vessels overexpressing αvβ3 integrin. Our polymer has a backbone of hydrophilic poly(ethylene glycol)-poly(L-glutamic acid) block copolymer, and cyclic RGD peptides are conjugated to side chains of the poly(L-glutamic acid) while IRDye 700DX is conjugated to the terminal of poly(ethylene glycol). The polymers exhibited selective accumulation to the target sites in a subcutaneous solid tumor, and the accumulation was augmented with the increased number of cyclic RGD peptides. More importantly, the polymer containing 15 cyclic RGD peptides in one construct revealed preferential accumulation on the tumor-associated blood vessels without compromising penetration to deep portions of the tumor, thereby drastically inhibiting tumor growth upon photoirradiation, while the polymer containing 5 cyclic RGD peptides showed moderate antitumor activity despite efficient accumulation in the tumor with almost homogenous intratumoral distribution. These results suggest that controlling the intratumoral distribution of IRDye 700DX is critical for successful PDT, and our polymer containing multiple cyclic RGD peptides may be a promising carrier for this spatial control.

Superabsorbent polymers (SAPs) are type of hydrogels capable to swell and absorb a large amount of water, but easily decomposed and oxidized by the air. We used electron-microscopic imaging in an indoor simulation with sand mulching to test the effects of various SAP concentrations on controlling evaporation and salt formation. The treatments were sand-mulched columns containing 0, 0.1, 0.2, 0.5 and 1.0% SAP. The soil particle pores were from dense to sparse and the corresponding fractal dimension decreased as SAP concentration increased. SAP concentration was correlated negatively with fractal dimension, clay-particle fraction and silt-volume fraction. And it showed a positive correlation with sand volume fraction. SAP concentration significantly affected the particle-size distribution. Water-storage capacity increased in each column layer (five 8-cm layers) at the same infiltration depth. Evaporation decreased the water content of each layer. Sand mulching combined with the SAP decreased evaporation in each layer relative to the control, which retained more water and decreased the accumulation of surface salt in the order 1.0% > 0.5% > 0.2% > 0.1% > 0. Salt migrated at 0-30 cm with sand mulching but 0-25 cm with sand mulching and SAP amendment. The decrease in salt accumulation was most effective at a SAP concentration of 0.2%.

Current treatment options for influenza virus infections in humans are limited and therefore the development of novel antivirals is of high priority. Inhibiting influenza virus attachment to host cells would provide an early and efficient block of the infection and thus, receptor analogs have been considered as options for antiviral treatment. Here, we describe the rapid and efficient synthesis of PAMAM dendrimers conjugated with either 3'-sialyllactose (3SL) or 6'-sialyllactose (6SL) and their potential to inhibit a diverse range of human and avian influenza virus strains. We show in a hemagglutination inhibition (HAI) assay that human IAV strains can be inhibited by (6SL)- and to a lesser extent also by (3SL)-conjugated PAMAM dendrimers. In contrast, avian strains could only be inhibited by (3SL)-conjugated dendrimers. Importantly, the differential sensitivities of human and avian IAV to the two types of sialyllactose-conjugated dendrimers could be confirmed in cell-based neutralization assays. Based on our findings, we suggest to further develop both, (3SL)- and (6SL)-conjugated PAMAM dendrimers, as influenza virus inhibitors.

Gene therapies represent a promising therapeutic route for liver cancers, but major challenges remain in the design of safe and efficient gene-targeting delivery systems. For example, cationic polymers show good transfection efficiency as gene carriers, but are hindered by cytotoxicity and non-specific targeting. Here we report a versatile method of one-step conjugation of glycyrrhetinic acid (GA) to reduce cytotoxicity and improve the cultured liver cell -targeting capability of cationic polymers. We have explored a series of cationic polymer derivatives by coupling different ratios of GA to polypropylenimine (PPI) dendrimer. These new gene carriers (GA-PPI dendrimer) were systematically characterized by UV-vis,(1)H NMR titration, electron microscopy, zeta potential, dynamic light-scattering, gel electrophoresis, confocal microscopy and flow cytometry. We demonstrate that GA-PPI dendrimers can efficiently load and protect pDNA, via formation of nanostructured GA-PPI/pDNA polyplexes. With optimal GA substitution degree (6.31%), GA-PPI dendrimers deliver higher liver cell transfection efficiency (43.5% vs 22.3%) and lower cytotoxicity (94.3% vs 62.5%, cell viability) than the commercial bench-mark DNA carrier bPEI (25 kDa) with cultured liver model cells (HepG2). There results suggest that our new GA-PPI dendrimer are a promising candidate gene carrier for targeted liver cancer therapy.

New biomaterials are sought for the development of bioengineered nanostructures. In the present study, electrospun nanofibers have been synthesized by using poly(methyl vinyl ether-alt-maleic acid) and poly(methyl vinyl ether-alt-maleic ethyl monoester) (PMVEMA-Ac and PMVEMA-ES, respectively) as building polymers for the first time. To further functionalize these materials, nanofibers of PMVEMA-Ac and PMVEMA-ES containing a conjugated polyelectrolyte (HTMA-PFP, blue emitter, and HTMA-PFNT, red emitter) were achieved with both forms maintaining a high solid state fluorescence yield without altered morphology. Also, 5-aminolevulinic acid (5-ALA) was incorporated within these nanofibers, where it remained chemically stable. In all cases, nanofiber diameters were less than 150 nm as determined by scanning and transmission electron microscopy, and encapsulation efficiency of 5-ALA was 97 ± 1% as measured by high-performance liquid chromatography. Both polymeric matrices showed rapid release kinetics in vertical cells (Franz cells) and followed Higuchi kinetics. In addition, no toxicity of nanofibers, in the absence of light, was found in HaCaT and SW480 cell lines. Finally, it was shown that loaded 5-ALA was functional, as it was internalized by cells in nanofiber-treated cultures and served as a substrate for the generation of protoporphyrin IX, suggesting these pharmaceutical vehicles are suitable for photodynamic therapy applications.

In this work, we present the synthesis and evaluation of magnetic resonance (MR) properties of novel phosphorus/iron-containing probes for dual 31P and 1H MR imaging and spectroscopy (MRI and MRS). The presented probes are composed of biocompatible semitelechelic and multivalent phospho-polymers based on poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC) coordinated with small paramagnetic Fe3+ ions or superparamagnetic maghemite (γ-Fe2O3) nanoparticles via deferoxamine group linked to the end or along the polymer chains. All probes provided very short 1H T1 and T2 relaxation times even at low iron concentrations. The presence of iron had a significant impact on the shortening of 31P relaxation, with the effect being more pronounced for probes based on γ-Fe2O3 and multivalent polymer. While the water-soluble probe having one Fe3+ ion per polymer chain was satisfactorily visualized by both 31P-MRS and 31P-MRI, the probe with multiple Fe3+ ions could only be detected by 31P-MRS, and the probes consisting of γ-Fe2O3 nanoparticles could not be imaged by either technique due to their ultra-short 31P relaxations. In this proof-of-principle study performed on phantoms at a clinically relevant magnetic fields, we demonstrated how the different forms and concentrations of iron affect both the 1H MR signal of the surrounding water molecules and the 31P MR signal of the phospho-polymer probe. Thus, this double contrast can be exploited to simultaneously visualize body anatomy and monitor probe biodistribution.

Bio-inspired conductive scaffolds composed of sodium hyaluronate containing a colloidal dispersion of water-miscible polyaniline or polypyrrole particles (concentrations of 0.108, 0.054 and 0.036% w/w) were manufactured. For this purpose, either crosslinking with N-(3-dimethylaminopropyl-N-ethylcarbodiimide hydrochloride and N-hydroxysuccinimid or a freeze-thawing process in the presence of poly(vinylalcohol) was used. The scaffolds comprised interconnected pores with prevailing porosity values of ~ 30% and pore sizes enabling the accommodation of cells. A swelling capacity of 92-97% without any sign of disintegration was typical for all samples. The elasticity modulus depended on the composition of the scaffolds, with the highest value of ~ 50 kPa obtained for the sample containing the highest content of polypyrrole particles. The scaffolds did not possess cytotoxicity and allowed cell adhesion and growth on the surface. Using the in vivo-mimicking conditions in a bioreactor, cells were also able to grow into the structure of the scaffolds. The technique of scaffold preparation used here thus overcomes the limitations of conductive polymers (e.g. poor solubility in an aqueous environment, and limited miscibility with other hydrophilic polymer matrices) and moreover leads to the preparation of cytocompatible scaffolds with potentially cell-instructive properties, which may be of advantage in the healing of damaged electro-sensitive tissues.

Supercapacitors (SCs) due to their high energy density, fast charge storage and energy transfer, long charge discharge curves and low costs are very attractive for designing new generation of energy storage devices. In this work we present a simple and scalable synthetic approach to engineer ternary composite as electrode material based on combination of graphene with doped metal oxides (iron oxide) and conductive polymer (polypyrrole) with aims to achieve supercapacitors with very high gravimetric and areal capacitances. In the first step a binary composite with graphene mixed with doped iron oxide (rGO/MeFe2O4) (Me = Mn, Ni) was synthesized using new single step process with NaOH acting as a coprecipitation and GO reducing agent. This rGO/MnFe2O4 composite electrode showed gravimetric capacitance of 147 Fg-1 and areal capacitance of 232 mFcm-2 at scan rate of 5 mVs-1. In the final step a conductive polypyrrole was included to prepare a ternary composite graphene/metal doped iron oxide/polypyrrole (rGO/MnFe2O4/Ppy) electrode. Ternary composite electrode showed significantly improved gravimetric capacitance and areal capacitance of 232 Fg-1 and 395 mFcm-2 respectively indicating synergistic impact of Ppy additives. The method is promising to fabricate advanced electrode materials for high performing supercapacitors combining graphene, doped iron oxide and conductive polymers.

Nucleic acid polymers (NAPs) block the release of subviral particles from hepatocytes, a mechanism consistent with their antiviral activity against hepatitis B virus (HBV) in patients. Analysis of immunostimulatory properties of NAPs were conducted with several NAP species: REP 2006, the prototypic degenerate NAP [dN]40, containing TLR9-stimulatory CpG; REP 2055 a clinically active NAP with a sequence [dAdC]20 devoid of CpG content; REP 2139 (also clinically active) and REP 2165 (REP 2055 analogues further rendered immunologically inactive by replacing cytidine with 5-methylcytidine and incorporating 2'-O methylation of riboses). These analyses revealed pro-inflammatory responses in human peripheral blood mononuclear cells with REP 2006 and with REP 2139 and REP 2165 only at high dose but displayed no significant antiviral activity. In primary isolated human hepatocytes and liver sinusoidal endothelial cells no significant inflammatory or antiviral responses were detected for any NAPs. In human Kupffer cells pro-inflammatory activity was observed with REP 2006 and REP 2055, whereas a weak but significant induction of interferon genes was only observed with REP 2006 at the highest concentration. We therefore hypothesize that the antiviral activity of NAPs optimized to treat HBV infection in patients cannot be explained by direct induction of innate antiviral responses.