Pirfenidone-Loaded Polymeric Micelles as an Effective Mechanotherapeutic to Potentiate Immunotherapy in Mouse Tumor Models.

Ongoing research is actively exploring the use of immune checkpoint inhibitors to treat solid tumors by inhibiting the PD-1/PD-L1 axis and reactivating the function of cytotoxic T effector cells. Many types of solid tumors, however, are characterized by a dense and stiff stroma and are difficult to treat. Mechanotherapeutics have formed a recent class of drugs that aim to restore biomechanical abnormalities of the tumor microenvironment, related to increased stiffness and hypo-perfusion. Here, we have developed a polymeric formulation containing pirfenidone, which has been successful in restoring the tumor microenvironment in breast tumors and sarcomas. We found that the micellar formulation can induce similar mechanotherapeutic effects to mouse models of 4T1 and E0771 triple negative breast tumors and MCA205 fibrosarcoma tumors but with a dose 100-fold lower than that of the free pirfenidone. Importantly, a combination of pirfenidone-loaded micelles with immune checkpoint inhibition significantly delayed primary tumor growth, leading to a significant improvement in overall survival and in a complete cure for the E0771 tumor model. Furthermore, the combination treatment increased CD4+ and CD8+ T cell infiltration and suppressed myeloid-derived suppressor cells, creating favorable immunostimulatory conditions, which led to immunological memory. Ultrasound shear wave elastography (SWE) was able to monitor changes in tumor stiffness during treatment, suggesting optimal treatment conditions. Micellar encapsulation is a promising strategy for mechanotherapeutics, and imaging methods, such as SWE, can assist their clinical translation.

3D Composite U(VI) Adsorbents Based on Alginate Hydrogels and Oxidized Biochar Obtained from Luffa cylindrica.

3D naturally derived composites consisting of calcium alginate hydrogels (CA) and oxidized biochar obtained from Luffa cylindrica (ox-LC) were synthesized and further evaluated as adsorbents for the removal of U(VI) from aqueous media. Batch-type experiments were conducted to investigate the effect of various physicochemical parameters on the adsorption performance of materials. The maximum adsorption capacity (qmax) was 1.7 mol kg-1 (404.6 mg·g-1) at pH 3.0 for the CA/ox-LC with a 10% wt. ox-LC content. FTIR spectroscopy indicated the formation of inner-sphere complexes between U(VI) and the surface-active moieties existing on both CA and ox-LC, while thermodynamic data revealed that the adsorption process was endothermic and entropy-driven. The experimental data obtained from the adsorption experiments were well-fitted by the Langmuir and Freundlich models. Overall, the produced composites exhibited enhanced adsorption efficiency against U(VI), demonstrating their potential use as effective adsorbents for the recovery of uranium ions from industrial effluents and seawater.

Iridium-Based Nanohybrids: Synthesis, Characterization, Optical Limiting, and Nonlinear Optical Properties.

The present work reports on the synthesis and characterization of iridium (Ir)-based nanohybrids with variable chemical compositions. More specifically, highly stable polyvinylpyrrolidone (PVP) nanohybrids of the PVP-IrO2 and PVP-Ir/IrO2 types, as well as non-coated Ir/IrO2 nanoparticles, are synthesized using different synthetic protocols and characterized in terms of their chemical composition and morphology via X-ray photoelectron spectroscopy (XPS) and scanning transmission electron microscopy (STEM), respectively. Furthermore, their nonlinear optical (NLO) response and optical limiting (OL) efficiency are studied by means of the Z-scan technique, employing 4 ns laser pulses at 532 and 1064 nm. The results demonstrate that the PVP-Ir/IrO2 and Ir/IrO2 systems exhibit exceptional OL performance, while PVP-IrO2 presents very strong saturable absorption (SA) behavior, indicating that the present Ir-based nanohybrids could be strong competitors to other nanostructured materials for photonic and optoelectronic applications. In addition, the findings denote that the variation in the content of IrO2 nanoparticles by using different synthetic pathways significantly affects the NLO response of the studied Ir-based nanohybrids, suggesting that the choice of the appropriate synthetic method could lead to tailor-made NLO properties for specific applications in photonics and optoelectronics.

Ofloxacin Removal from Aqueous Media by Means of Magnetoactive Electrospun Fibrous Adsorbents.

Functionalized electrospun polymer microfibrous membranes were fabricated by electrospinning and further surface-functionalized with magnetic iron oxide (FexOy) nanoparticles to yield magnetoactive nanocomposite fibrous adsorbents. The latter were characterized in respect to their morphology, mechanical properties and magnetic properties while they were further evaluated as substrates for removing Ofloxacin (OFL) from synthetic aqueous media and secondary urban wastewater (UWW) under varying physicochemical parameters, including the concentration of the pharmaceutical pollutant, the solution pH and the membranes' magnetic content. The magnetic-functionalized fibrous adsorbents demonstrated significantly enhanced adsorption efficacy in comparison to their non-functionalized fibrous analogues while their magnetic properties enabled their magnetic recovery and regeneration.

Functionalized Magnetic Nanomaterials in Agricultural Applications.

The development of functional nanomaterials exhibiting cost-effectiveness, biocompatibility and biodegradability in the form of nanoadditives, nanofertilizers, nanosensors, nanopesticides and herbicides, etc., has attracted considerable attention in the field of agriculture. Such nanomaterials have demonstrated the ability to increase crop production, enable the efficient and targeted delivery of agrochemicals and nutrients, enhance plant resistance to various stress factors and act as nanosensors for the detection of various pollutants, plant diseases and insufficient plant nutrition. Among others, functional magnetic nanomaterials based on iron, iron oxide, cobalt, cobalt and nickel ferrite nanoparticles, etc., are currently being investigated in agricultural applications due to their unique and tunable magnetic properties, the existing versatility with regard to their (bio)functionalization, and in some cases, their inherent ability to increase crop yield. This review article provides an up-to-date appraisal of functionalized magnetic nanomaterials being explored in the agricultural sector.

Superparamagnetic electrospun microrods for magnetically-guided pulmonary drug delivery with magnetic heating.

Controlled pulmonary drug delivery systems employing non-spherical particles as drug carriers attract considerable attention nowadays. Such anisotropic morphologies may travel deeper into the lung airways, thus enabling the efficient accumulation of therapeutic compounds at the point of interest and subsequently their sustained release. This study focuses on the fabrication of electrospun superparamagnetic polymer-based biodegradable microrods consisting of poly(l-lactide) (PLLA), polyethylene oxide (PEO) and oleic acid-coated magnetite nanoparticles (OA·Fe3O4). The production of magnetite-free (0% wt. OA·Fe3O4) and magnetite-loaded (50% and 70% wt. Fe3O4) microrods was realized upon subjecting the as-prepared electrospun fibers to UV irradiation, followed by sonication. Moreover, drug-loaded microrods were fabricated incorporating methyl 4-hydroxybenzoate (MHB) as a model pharmaceutical compound and the drug release profile from both, the drug-loaded membranes and the corresponding microrods was investigated in aqueous media. In addition, the magnetic properties of the produced materials were exploited for remote induction of hyperthermia under AC magnetic field, while the possibility to reduce transport losses and enhance the targeted delivery to lower airways by manipulation of the airborne microrods by DC magnetic field was also demonstrated.

From Single-Core Nanoparticles in Ferrofluids to Multi-Core Magnetic Nanocomposites: Assembly Strategies, Structure, and Magnetic Behavior.

Iron oxide nanoparticles are the basic components of the most promising magnetoresponsive nanoparticle systems for medical (diagnosis and therapy) and bio-related applications. Multi-core iron oxide nanoparticles with a high magnetic moment and well-defined size, shape, and functional coating are designed to fulfill the specific requirements of various biomedical applications, such as contrast agents, heating mediators, drug targeting, or magnetic bioseparation. This review article summarizes recent results in manufacturing multi-core magnetic nanoparticle (MNP) systems emphasizing the synthesis procedures, starting from ferrofluids (with single-core MNPs) as primary materials in various assembly methods to obtain multi-core magnetic particles. The synthesis and functionalization will be followed by the results of advanced physicochemical, structural, and magnetic characterization of multi-core particles, as well as single- and multi-core particle size distribution, morphology, internal structure, agglomerate formation processes, and constant and variable field magnetic properties. The review provides a comprehensive insight into the controlled synthesis and advanced structural and magnetic characterization of multi-core magnetic composites envisaged for nanomedicine and biotechnology.

Engineered magnetoactive collagen hydrogels with tunable and predictable mechanical response.

In the present study, the synthesis of superparamagnetic collagen-based nanocomposite hydrogels with tunable swelling, mechanical and magnetic properties is reported. The fabrication strategy involved the preparation of pristine collagen type-I hydrogels followed by their immersion in highly stable aqueous solutions containing pre-formed double-layer oleic acid-coated hydrophilic magnetite nanoparticles (OA.OA.Fe3O4) at different concentrations, to interrogate nanoparticles' deposition within the 3D fibrous collagen matrix. Besides the investigation of the morphology, composition and magnetic properties of the produced materials, their mechanical properties were experimentally evaluated under confined compressive loading conditions while an exponential constitutive equation was employed to describe their mechanical response. Moreover, the deposition of the nanoparticles in the collagenous matrix was modeled mathematically with respect to the swelling of the gel and the effective stiffness of the matrix. The model recapitulated nanoparticle diffusion and deposition as well as hydrogel swelling, in terms of nanoparticles' size and concentration of OA.OA.Fe3O4 aqueous solution.

Multifunctional Gas and pH Fluorescent Sensors Based on Cellulose Acetate Electrospun Fibers Decorated with Rhodamine B-Functionalised Core-Shell Ferrous Nanoparticles.

Ferrous core-shell nanoparticles consisting of a magnetic γ-Fe2O3 multi-nanoparticle core and an outer silica shell have been synthesized and covalently functionalized with Rhodamine B (RhB) fluorescent molecules (γ-Fe2O3/SiO2/RhB NPs). The resulting γ-Fe2O3/SiO2/RhB NPs were integrated with a renewable and naturally-abundant cellulose derivative (i.e. cellulose acetate, CA) that was processed in the form of electrospun fibers to yield multifunctional fluorescent fibrous nanocomposites. The encapsulation of the nanoparticles within the fibers and the covalent anchoring of the RhB fluorophore onto the nanoparticle surfaces prevented the fluorophore's leakage from the fibrous mat, enabling thus stable fluorescence-based operation of the developed materials. These materials were further evaluated as dual fluorescent sensors (i.e. ammonia gas and pH sensors), demonstrating consistent response for very high ammonia concentrations (up to 12000 ppm) and fast and linear response in both alkaline and acidic environments. The superparamagnetic nature of embedded nanoparticles provides means of electrospun fibers morphology control by magnetic field-assisted processes and additional means of electromagnetic-based manipulation making possible their use in a wide range of sensing applications.

Uranium adsorption by polyvinylpyrrolidone/chitosan blended nanofibers.

PVP/chitosan blended nanofibers have been prepared and investigated as adsorbent material for the removal of hexavalent uranium (U(VI)) from aqueous solutions. The nanofibers have been characterized prior and after U(VI) adsorption by SEM and FTIR measurements, and the effect of various parameters such as metal-ion concentration temperature and contact time on the adsorption efficiency has been investigated by batch-type experiments. The material presents increased sorption capacity (qmax= (167 ± 25) g kg-1 at pH 6.0) and increased chemical affinity for U(VI), which is attributed to the fibrous structure of the material and the presence of polar groups (e.g. carbonyl groups) on the blended nanofibers. FTIR spectroscopic measurements indicate the formation of inner sphere complexes between U(VI) and the surface moieties, and thermodynamic and kinetic data reveal a relatively fast (k1 = 0.01 min-1), entropy-driven process (ΔHo = 56.3 kJ mol-1 and ΔSo = 293.7 J K-1 mol-1). Recycling experiments have shown that the material can be used up to four times with less than 10% efficiency loss.

Fluorescent electrospun PMMA microfiber mats with embedded NaYF4: Yb/Er upconverting nanoparticles.

Functional upconverting nanoparticles (UCNPs) can offer new possibilities in fluorescent applications as they exhibit desired characteristic properties like large shift between the fluorescent emission signal and the infrared excitation wavelength, multi- and narrow-band absorption and emission in visible and near infrared - Vis/NIR, together with excellent photostability and low toxicity as opposed to semiconducting quantum dots. The upconversion luminescence emission or quenching characteristics of UCNPs can be altered upon exposure to physical or chemical environmental factors providing thus a functionality that can be utilized for sensing or imaging. Furthermore their functionalization with suitable indicator dyes or recognition elements can extend the range of luminescence response and ratiometric sensing to specific analytes. Synergistically, electrospun nano- and microfibers offering large surface area can enhance the functionality of UCNPs by retaining the fluorescence efficiency and improving the overall responsivity due to dramatically increased surface. For the optimization of this hybrid material system the controllable incorporation of UCNPs is required especially at increased concentration conditions needed for high brightness. Herein, we report the fabrication, morphological and optical characterization of electrospun polymer-based nanocomposite fibers, consisting of poly(methyl methacrylate) (PMMA) and upconverting lanthanide doped nanoparticles of the type NaYF4 : 20% Yb3+/2% Er3+ @ NaYF4. Morphological studies regarding the uniformity and aggregation effects of the UCNP inclusion within the fibers have been implemented followed by upconversion emission characterization by pulsed near-infrared excitation. The study and optimization of such nanocomposite fibrous systems could provide useful insights for the development of efficient upconverting electrospun fiber mats for a number of imaging and sensing applications.

Robust Hydrophobic and Hydrophilic Polymer Fibers Sensitized by Inorganic and Hybrid Lead Halide Perovskite Nanocrystal Emitters.

Advances in the technology and processing of flexible optical materials have paved the way toward the integration of semiconductor emitters and polymers into functional light emitting fabrics. Lead halide perovskite nanocrystals appear as highly suitable optical sensitizers for such polymer fiber emitters due to their ease of fabrication, versatile solution-processing and highly efficient, tunable, and narrow emission across the visible spectrum. A beneficial byproduct of the nanocrystal incorporation into the polymer matrix is that it provides a facile and low-cost method to chemically and structurally stabilize the perovskite nanocrystals under ambient conditions. Herein, we demonstrate two types of robust fiber composites based on electrospun hydrophobic poly(methyl methacrylate) (PMMA) or hydrophilic polyvinylpyrrolidone (PVP) fibrous membranes sensitized by green-emitting all-inorganic CsPbBr3 or hybrid organic-inorganic FAPbBr3 nanocrystals. We perform a systematic investigation on the influence of the nanocrystal-polymer relative content on the structural and optical properties of the fiber nanocomposites and we find that within a wide content range, the nanocrystals retain their narrow and high quantum yield emission upon incorporation into the polymer fibers. Quenching of the radiative recombination at the higher/lower bound of the nanocrystal:polymer mass ratio probed is discussed in terms of nanocrystal clustering/ligand desorption due to dilution effects, respectively. The nanocomposite's optical stability over an extended exposure in air and upon immersion in water is also discussed. The studies confirm the demonstration of robust and bright polymer-fiber emitters with promising applications in backlighting for LCD displays and textile-based light emitting devices.

Electrohydrodynamic methods for the development of pulmonary drug delivery systems.

Electrospinning and electrospraying are two highly versatile and scalable electrohydrodynamic methods, which have attracted considerable attention during the last years towards the fabrication of polymer-based drug delivery systems. The latter may be obtained in the form of nano- or microfibers (via electrospinning) or as drug-loaded nano- and microparticles (via electrospraying). This review article begins with an introduction on the basic principles and the important influencing parameters governing the electrospinning/electrospraying processes, followed by an overview on their use for the development of nano/microfibers and nano/microparticles destined for use in pharmaceutical applications. Focus is given on research efforts targeting in the formulation of drug delivery systems and devices designed for pulmonary drug delivery applications thus emphasizing on the potential use of electrospinning and electrospraying in the area of inhaled medicines.

Structure and Magnetic Property Control of Copper Hydroxide Acetate by Non-Classical Crystallization.

Copper hydroxide acetate (CHA), one layered hydroxide compound with tunable magnetism, attracts great interest because of its potential applications in memory devices. However, ferromagnetism for CHA is only demonstrated by means of GPa pressure. Herein, a new method is reported, involving the combination of different crystallization pathways to control crystallization of amorphous CHA toward the formation of CHA/polymer composites with tunable magnetic properties and even a tunability that can be tested at room temperature. By using poly[(ethylene glycol)6 methyl ether methacrylate]-block-poly[2-(acetoacetoxy) ethyl methacrylate] (PEGMA-b-PAEMA) diblock copolymers as additives in combination with a post-treatment process by ultracentrifugation, it is demonstrated that CHA and PEGMA-b-PAEMA form composites exhibiting different magnetic properties, depending on CHA in-plane nanostructures. Analytical characterization reveals that crystallization of CHA is induced by ultracentrifugation, during which CHA nanostructures can be well controlled by changing the degrees of polymerization of the PEGMA and PAEMA blocks and their block length ratios. These findings not only present the first example of using crystallization from polymer stabilized amorphous precursors toward the generation of magnetic nanomaterials with tunable magnetism but also pave the way for the future design of functional composite materials.

Evaluation of PVP/Au Nanocomposite Fibers as Heterogeneous Catalysts in Indole Synthesis.

Electrospun nanocomposite fibers consisting of crosslinked polyvinylpyrrolidone (PVP) chains and gold nanoparticles (Au NPs) were fabricated, starting from highly stable PVP/Au NP colloidal solutions with different NP loadings, followed by thermal treatment. Information on the morphological characteristics of the fibers and of the embedded Au NPs was obtained by electron microscopy. Cylindrical, bead-free fibers were visualized by Scanning Electron Microscopy (SEM) while Transmission Electron Microscopy (TEM) and Energy Diffraction X-ray (EDX) analysis supported the presence of Au NPs within the fibers and gave information on their morphologies and average diameters. These materials were briefly evaluated as heterogeneous catalytic supports for the gold-catalyzed intramolecular cyclisation of 2­(phenylethynyl)aniline to form 2-phenyl-1H-indole. The performance of the gold catalyst was strongly dependent on the Au NP size, with the system containing the smallest Au NPs being the more effective. Moreover, a slight drop of their catalytic efficiency was observed after three consecutive reaction runs, which was attributed to morphological changes as a consequence of fiber merging.

Semi-Interpenetrating Polymer Networks with Predefined Architecture for Metal Ion Fluorescence Monitoring.

The development of new synthetic approaches for the preparation of efficient 3D luminescent chemosensors for transition metal ions receives considerable attention nowadays, owing to the key role of the latter as elements in biological systems and their harmful environmental effects when present in aquatic media. In this work, we describe an easy and versatile synthetic methodology that leads to the generation of nonconjugated 3D luminescent semi-interpenetrating amphiphilic networks (semi-IPN) with structure-defined characteristics. More precisely, the synthesis involves the encapsulation of well-defined poly(9-anthrylmethyl methacrylate) (pAnMMA) (hydrophobic, luminescent) linear polymer chains within a covalent poly(2-(dimethylamino)ethyl methacrylate) (pDMAEMA) hydrophilic polymer network, derived via the 1,2-bis-(2-iodoethoxy)ethane (BIEE)-induced crosslinking process of well-defined pDMAEMA linear chains. Characterization of their fluorescence properties demonstrated that these materials act as strong blue emitters when exposed to UV irradiation. This, combined with the presence of the metal-binding tertiary amino functionalities of the pDMAEMA segments, allowed for their applicability as sorbents and fluorescence chemosensors for transition metal ions (Fe3+, Cu2+) in solution via a chelation-enhanced fluorescence-quenching effect promoted within the semi-IPN network architecture. Ethylenediaminetetraacetic acid (EDTA)-induced metal ion desorption and thus material recyclability has been also demonstrated.

Low temperature and cost-effective growth of vertically aligned carbon nanofibers using spin-coated polymer-stabilized palladium nanocatalysts.

We describe a fast and cost-effective process for the growth of carbon nanofibers (CNFs) at a temperature compatible with complementary metal oxide semiconductor technology, using highly stable polymer-Pd nanohybrid colloidal solutions of palladium catalyst nanoparticles (NPs). Two polymer-Pd nanohybrids, namely poly(lauryl methacrylate)-block-poly((2-acetoacetoxy)ethyl methacrylate)/Pd (LauMA x -b-AEMA y /Pd) and polyvinylpyrrolidone/Pd were prepared in organic solvents and spin-coated onto silicon substrates. Subsequently, vertically aligned CNFs were grown on these NPs by plasma enhanced chemical vapor deposition at different temperatures. The electrical properties of the grown CNFs were evaluated using an electrochemical method, commonly used for the characterization of supercapacitors. The results show that the polymer-Pd nanohybrid solutions offer the optimum size range of palladium catalyst NPs enabling the growth of CNFs at temperatures as low as 350 °C. Furthermore, the CNFs grown at such a low temperature are vertically aligned similar to the CNFs grown at 550 °C. Finally the capacitive behavior of these CNFs was similar to that of the CNFs grown at high temperature assuring the same electrical properties thus enabling their usage in different applications such as on-chip capacitors, interconnects, thermal heat sink and energy storage solutions.

Fabrication, characterization, and evaluation in drug release properties of magnetoactive poly(ethylene oxide)-poly(L-lactide) electrospun membranes.

The fabrication of electrospun magnetoactive fibrous nanocomposite membranes based on the water-soluble and biocompatible poly(ethylene oxide) (PEO), the biocompatible and biodegradable poly(L-lactide) (PLLA) and preformed oleic acid-coated magnetite nanoparticles (OA.Fe3O4) is reported. Visualization of the membranes by electron microscopy techniques reveals the presence of continuous fibers of approximately 2 µm in diameter, with the magnetic nanoparticles being evenly distributed within the fibers, retaining at the same time their nanosized diameters (≈ 5 nm). Thermal gravimetric analysis measurements suggest that the magnetic nanoparticles embedded within the polymer fibers affect favorably the thermal stability of the membranes. Moreover, assessment of their magnetic characteristics by vibrating sample magnetometry discloses tunable superparamagnetic behavior at ambient temperature. For the first time, the biocompatibility and biodegradability of PEO/PLLA and the tunable magnetic activity of the OA.Fe3O4 are combined in the same drug delivery system, with N-acetyl-p-aminophenol (acetaminophen) as a proof-of-concept pharmaceutical. Furthermore, their heating ability under alternating current (AC) magnetic field conditions is evaluated using frequency of 110 kHz and corresponding magnetic field strength of 25 mT (19.9 kA/m). Consequently, these magnetoactive fibrous nanocomposites exhibit promising characteristics for future exploitation in magnetothermally triggered drug delivery.

Polymeric theranostics: using polymer-based systems for simultaneous imaging and therapy.

Polymer-based nanomedicine is a large and fast growing field. Polymer-based systems have been extensively used as therapeutic carriers as well as bioimaging agents for example in tumour diagnosis. However, fewer polymeric systems have been able to combine both therapy and imaging in a new field that is called theranostics (theragnostics). This review aims to summarise the recent developments and trends on polymeric theranostics. Four different types of therapies/treatments are examined namely drug delivery, gene delivery, photodynamic therapy and hyperthermia treatment combined with different imaging moieties like magnetic resonance imaging agents, fluorescent agents and microbubbles for ultrasound imaging.

Multiresponsive polymer conetworks capable of responding to changes in pH, temperature, and magnetic field: synthesis, characterization, and evaluation of their ability for controlled uptake and release of solutes.

This study deals with the preparation of novel multiresponsive (magnetoresponsive, thermoresponsive and pH-responsive) nanocomposite conetworks consisting of oleic acid-coated magnetite nanoparticles (OA·Fe(3)O(4)), hydrophilic/thermoresponsive hexa(ethylene glycol) methyl ether methacrylate (HEGMA), hydrophobic/metal binding 2-(acetoacetoxy)ethyl methacrylate (AEMA), and pH-responsive/thermoresponsive N-diethylaminoethyl methacrylate (DEAEMA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) moieties. Conventional free radical copolymerization was employed for the synthesis of random conetworks in the absence and presence of preformed OA·Fe(3)O(4). Further, in characterization of these materials in regards to their swelling behavior in organic and aqueous solvents, thermal/thermoresponsive properties, and composition, assessment of their magnetic characteristics disclosed tunable superparamagnetic behavior. These systems were also evaluated toward their ability to adsorb and release a solute (benzoic acid) in a controlled manner upon varying the pH.