Pharmacological Effects of Astragaloside IV: A Review.

Astragaloside IV (AS-IV) is one of the main active components extracted from the Chinese medicinal herb Astragali and serves as a marker for assessing the herb's quality. AS-IV is a tetracyclic triterpenoid saponin in the form of lanolin ester alcohol and exhibits various biological activities. This review article summarizes the chemical structure of AS-IV, its pharmacological effects, mechanism of action, applications, future prospects, potential weaknesses, and other unexplored biological activities, aiming at an overall analysis. Papers were retrieved from online electronic databases, such as PubMed, Web of Science, and CNKI, and data from studies conducted over the last 10 years on the pharmacological effects of AS-IV as well as its impact were collated. This review focuses on the pharmacological action of AS-IV, such as its anti-inflammatory effect, including suppressing inflammatory factors, increasing T and B lymphocyte proliferation, and inhibiting neutrophil adhesion-associated molecules; antioxidative stress, including scavenging reactive oxygen species, cellular scorching, and regulating mitochondrial gene mutations; neuroprotective effects, antifibrotic effects, and antitumor effects.

Synergistic Targeting and Efficient Photodynamic Therapy Based on Graphene Oxide Quantum Dot-Upconversion Nanocrystal Hybrid Nanoparticles.

Locating nanotherapeutics at the active sites, especially in the subcellular scale, is of great importance for nanoparticle-based photodynamic therapy (PDT) and other nanotherapies. However, subcellular targeting agents are generally nonspecific, despite the fact that the accumulation of a nanoformulation at active organelles leads to better therapeutic efficacy. A PDT nanoformulation is herein designed by using graphene oxide quantum dots (GOQDs) with rich functional groups as both the supporter for dual targeting modification and the photosensitizer for generating reactive oxygen species, and upconversion nanoparticles (UCNs) as the transducer of excitation light. A tumor-targeting agent, folic acid, and a mitochondrion-targeting moiety, carboxybutyl triphenylphosphonium, are simultaneously attached onto the UCNs-GOQDs hybrid nanoparticles by surface modification, and a synergistic targeting effect is obtained for these nanoparticles according to both in vitro and in vivo experiments. More significant cell death and a higher extent of mitochondrion damage are observed compared to the results of UCNs-GOQDs nanoparticles with no or just one targeting moiety. Furthermore, the PDT efficacy on tumor-bearing mice is also effectively improved. Overall, the current work presents a synergistic strategy to enhance subcellular targeting and the PDT efficacy for cancer therapy, which may also shed light on other kinds of nanotherapies.

Lysine-derived, pH-sensitive and biodegradable poly(beta-aminoester urethane) networks and their local drug delivery behaviour.

In this study, a series of covalently crosslinked, l-lysine based poly(beta-aminoester urethane) (LPBAEU) networks with good biodegradability and pH sensitivity was reported. The effect of hydrophilic/hydrophobic characteristics and diacrylate/amine molar ratio on the structure, swelling and degradation behaviour of the networks was investigated. The water transport mechanism and dynamic swelling behavior of the LPBAEU networks were strongly affected by medium pH, and swelling amounts up to 252.2% and 148.7% were observed at pH 5.6 and pH 7.4, respectively. It was found that water diffusion within the networks followed a non-Fickian mechanism. The LPBAEU network with the highest diacrylate/amine molar ratio exhibited the highest tensile strength and Young's modulus. In vitro mass losses of networks showed that the degradation rate of LPBAEU networks can be adjusted from 4 to 14 days. LPBAEU networks also supported loading of doxycycline hyclate (DH) and in vitro release studies demonstrated that release of DH from the networks was substantially hindered in the neutral pH environment, with 20.9-56.2% DH release, whereas DH release was accelerated under mild acidic conditions, with a release percentage of 36.6-99.6%. The release data were fitted to different mathematical models and the obtained results confirmed that these networks released DH in a non-Fickian mechanism. The results of this research support the idea that pH-responsive LPBAEU networks may find potential applications in local drug delivery.

Efficacy Dependence of Photodynamic Therapy Mediated by Upconversion Nanoparticles: Subcellular Positioning and Irradiation Productivity.

Singlet oxygen (1 O2 ), as an important kind of reactive oxygen species (ROS) and main therapeutic agent in photodynamic therapy (PDT), only have a half-life of 40 ns and an effective radius of 20 nm, which cause significant obstacles for improving PDT efficacy. In this work, novel upconversion nanoparticle (UCN)-based nanoplatforms are developed with a minimized distance between UCNs and a photosensitizer, protoporphyrin IX (PpIX), and a controllable payload of PpIX, to enhance and control ROS production. The ability of the nanoplatform to target different subcellular organelles such as cell membrane and mitochondria is demonstrated via surface modification of the nanoplatform with different targeting ligands. The results show that the mitochondria-targeting nanoplatforms result in significantly increased capability of both tumor cell killing and inhibition of tumor growth. Subcellular targeting of nanoparticles leads to the death of cancer cells in different manners. However, the efficiency of ROS generation almost have no influence on the tumor cell viability during the period of evaluation. These findings suggest that specific subcellular targeting of the nanoplatforms enhances the PDT efficacy more effectively than the increase of ROS production, and may shed light on future novel designs of effective and controllable PDT nanoplatforms.

Photocontrolled Release of Doxorubicin Conjugated through a Thioacetal Photocage in Folate-Targeted Nanodelivery Systems.

Despite their proven ability for precise and targeted release, nanoplatform systems for photocontrolled delivery often face formidable synthetic challenges, in part due to the paucity of advanced linker strategies. Here, we report on a novel linker strategy using a thioacetal ortho-nitrobenzaldehyde (TNB) cage, demonstrating its application for delivery of doxorubicin (Dox) in two nanoscale systems. This photocleavable linker, TNB(OH), which presents two identical arms, each terminated with a hydroxyl functionality, was prepared in a single step from 6-nitroveratraldehyde. TNB(OH) was used to cross-link Dox to a folate receptor (FAR)-targeting poly(amidoamine) dendrimer conjugate G5(FA)n=5.4(Dox)m=5.1, and also used to prepare an upconversion nanocrystal (UCN) conjugate, UCN-PPIX@(Dox)(G5FA), a larger core/shell nanostructure. In this core/shell nanostructure, the UCN core emits UV and visible light luminescence upon near-infrared (NIR) excitation, allowing for the photocleavage of the TNB linker as well as the photostimulation of protoporphyrin IX (PPIX) coupled as a cytotoxic photosensitizer. Drug-release experiments performed in aqueous solutions with long-wavelength ultraviolet A (UVA) light showed that Dox release occurred rapidly from its TNB linked form or from its dendrimer conjugated form with comparable decay kinetics. Cellular toxicity studies in FAR-overexpressing KB carcinoma cells demonstrated that each nanoconjugate lacked intrinsic cytotoxicity until exposed to UVA or NIR (980 nm) (for the UCN nanoconjugate), which resulted in induction of potent cytotoxicity. In summary, this new TNB strategy offers synthetic convenience in drug conjugation chemistry with the ability for the temporal control of drug activation at the delivery site.

Mechanically adaptive and shape-memory behaviour of chitosan-modified cellulose whisker/elastomer composites in different pH environments.

Biomimetic polymer composites with water-active mechanically adaptive and shape-memory behaviour in different pH environments are synthesised by using chitosan-modified cellulose whiskers (CS-CWs) as the stimulus-responsive phase and thermoplastic polyurethane (TPU) as the resilient matrix. The effect of surface modification on the mechanically adaptive behaviour of CS-CW/TPU composites is investigated by using three representative solutions with various pH values. The results show that surface modification significantly enhances the modulus contrast under wet and dry conditions with the acidic solution as the stimulus, while maintaining the high modulus contrast with the basic solution as the stimulus. CS-CW/TPU composites also exhibit excellent shape-memory effects in all three solutions that are comparable to those pristine CW/TPU composites. Furthermore, activation of force generation in the stretched CS-CW/TPU composites by water absorption/desorption was observed.

Poly(glycerol sebacate urethane)-cellulose nanocomposites with water-active shape-memory effects.

Biodegradable and biocompatible materials with shape-memory effects (SMEs) are attractive for use as minimally invasive medical devices. Nanocomposites with SMEs were prepared from biodegradable poly(glycerol sebacate urethane) (PGSU) and renewable cellulose nanocrystals (CNCs). The effects of CNC content on the structure, water absorption, and mechanical properties of the PGSU were studied. The water-responsive mechanically adaptive properties and shape-memory performance of PGSU-CNC nanocomposites were observed, which are dependent on the content of CNCs. The PGSU-CNC nanocomposite containing 23.2 vol % CNCs exhibited the best SMEs among the nanocomposites investigated, with the stable shape fixing and shape recovery ratios being 98 and 99%, respectively, attributable to the formation of a hydrophilic, yet strong, CNC network in the elastomeric matrix. In vitro degradation profiles of the nanocomposites were assessed with and without the presence of an enzyme.

Modulating the Properties of Poly(glycerol sebacate)-Based Polyurethane Hydrogels Using an Organoclay.

Elastomeric hydrogels are promising in soft tissue applications due to their biomimetic mechanical and physical behaviors. In this study, we design and synthesize a poly(glycerol sebacate)-based polyurethane-clay nanocomposite hydrogel system with controllable mechanical, swelling, drug release, and biodegradation behaviors. The polymer-clay nanocomposites are synthesized by in situ polymerization in the presence of a solvent, which facilitates the dispersion of clay within the polymer matrix and their bonding. The nanocomposite hydrogels exhibit higher water swelling ratios in comparison to the neat polymer. The fully swollen hydrogels are capable of enduring complex mechanical deformations such as stretching and knotting, while the tensile moduli of the hydrogels mimic various soft tissues in human body. The mechanical behavior of hydrogels is significantly enhanced by the addition of no more than 3 phr clay, showing higher stiffness, strength, ductility, and toughness. The drug loading and release behavior of the hydrogels is investigated with three model drugs, showing selective drug loading capacity and sustained release, based on the Coulombic interaction between the clay and drug molecules. Biodegradation tests under a simulated body condition reveal a highly tunable degradation rate by the clay content in the nanocomposite hydrogels. Good cytocompatibility by the cell metabolic assay with mouse fibroblasts in vitro is also demonstrated. Finally, three-dimensional microporous foam is manufactured as a proof-of-concept study.

Wholly Biobased, Highly Stretchable, Hydrophobic, and Self-healing Thermoplastic Elastomer.

Renewable polymers with excellent stretchability and self-healing ability are interesting for a wide range of applications. A novel type of wholly biobased, self-healing, polyamide-based thermoplastic elastomer was synthesized using a fatty dimer acid and a fatty dimer amine, both containing multiple alkyl chains, through facile one-pot condensation polymerization under different polymerization times. The resulting elastomer shows superior stretchability (up to 2286%), high toughness, and excellent shape recovery after being stretched to different strains. This elastomer also displays high room-temperature autonomous self-healing efficiency after fracture and zero water uptake during water immersion. The highly entangled main chain, the multiple dangling chains, the abundant reversible physical bonds, the intermolecular diffusion, and the low ratio of amide to methylene group within the elastomer are responsible for these extraordinary properties. The polymerization time influences the properties of the elastomer. The use of the optimal self-healing thermoplastic elastomer in anticorrosion coating, piezoresistive sensing, and highly stretchable fibers is also demonstrated. The elastomer coating prevents stainless-steel products from corrosion in a salty environment due to its superhydrophobicity. The elastomer serves as a robust flexible substrate for creating self-healing piezoresistive sensors with excellent repeatability and self-healing efficiency. The elastomer fiber yarn can be stretched to 950% of its original length confirming its outstanding stretchability.

Surface interactions and viability of coronaviruses.

The recently emerged coronavirus pandemic (COVID-19) has become a worldwide threat affecting millions of people, causing respiratory system related problems that can end up with extremely serious consequences. As the infection rate rises significantly and this is followed by a dramatic increase in mortality, the whole world is struggling to accommodate change and is trying to adapt to new conditions. While a significant amount of effort is focused on developing a vaccine in order to make a game-changing anti-COVID-19 breakthrough, novel coronavirus (SARS-CoV-2) is also developing mutations rapidly as it transmits just like any other virus and there is always a substantial chance of the invented antibodies becoming ineffective as a function of time, thus failing to inhibit virus-to-cell binding efficiency as the spiked protein keeps evolving. Hence, controlling the transmission of the virus is crucial. Therefore, this review summarizes the viability of coronaviruses on inanimate surfaces under different conditions while addressing the current state of known chemical disinfectants for deactivation of the coronaviruses. The review attempts to bring together a wide spectrum of surface-virus-cleaning agent interactions to help identify material selection for inanimate surfaces that have frequent human contact and cleaning procedures for effective prevention of COVID-19 transmission.

Tailoring conductive network nanostructures of ZIF-derived cobalt-decorated N-doped graphene/carbon nanotubes for microwave absorption applications.

Confronted with microwave pollution issues, there is an urgent need for microwave absorption materials that possess optimal combinations of dielectric loss and magnetic loss properties. While a variety of studies focus on the components, the construction of nanostructure is rarely studied, which is of equivalent significance to microwave absorber design. In this work, Co-ZIF-67 was adopted as self-template to grow N-doped graphene/carbon nanotube interlinked conductive networks in-situ under a one-step carbonization process with tailored microwave absorption properties. Diverse microwave absorption performance could be achieved by directly adjusting the proportions among ingredients and the calcination temperature, obtaining a maximum value of reflection loss of -65.45 dB at 17.5 GHz with a sample thickness of just 1.5 mm. The effective absorption bandwidth could be tailored from 3.75 to 18 GHz among different thickness as required. The nanostructures had an apparent impact on the corresponding microwave absorption performance, in which the N-doped carbon-based conductive networks, ferromagnetic cobalt atoms, and interfaces among heterostructure strengthened the dipolar polarization and conductivity loss, magnetic loss, and interfacial polarization, respectively. This synthesis strategy offers a promising pathway for integrating nanostructures and functions, catering to requirements for designing and optimizing prospective microwave absorbers.

The effect of porous structure on the cell proliferation, tissue ingrowth and angiogenic properties of poly(glycerol sebacate urethane) scaffolds.

Novel, porous, biodegradable biomaterials which support tissue integration and angiogenesis and which have elastomeric properties are needed to repair and replace soft tissues in dynamic environments. In this study poly(glycerol sebacate urethane) (PGSU) scaffolds with different porous structures were fabricated using freeze-drying by varying the polymer concentration of the freeze-drying solution, during which the polymer was further crosslinked. The effect of the porous structure on the physical properties, cell proliferation, tissue ingrowth and angiogenic properties was investigated. By increasing the polymer concentration in the freeze-drying solution from 5 w/v% to 10 w/v% and 15 w/v%, the porosity and pore size of the scaffold decreased, resulting in porosities ranging between 88 - 96% and pore sizes 6.4-28.2 µm. The mechanical properties increased with the polymer concentration, with ultimate tensile strength and Young's modulus between 0.05 - 0.86 MPa and 0.05-0.65 MPa respectively and negligible loss of tensile strength after 100 cycles of loading. Enzymatic degradation over 28 days demonstrated linear degradation kinetics with mass loss between 19.1 - 52.3%. All PGSU scaffolds provided a viable environment for cell attachment, in which cell metabolic activity increased over time indicating cell proliferation. The cells adhered to PGSU scaffolds produced and deposited high quantities of collagen, reaching 7.5% of the sample's dry mass after 14 days culture for the scaffold with the highest porosity. Additionally, the scaffolds with the polymer concentration of 5 w/v% implanted onto the chick chorioallantoic membrane supported rapid tissue ingrowth and new blood vessel formation within the porous scaffold. These results demonstrate that PGSU scaffolds have potential for use in many areas of soft tissue engineering.

Viral filtration using carbon-based materials.

Viral infections alone are a significant cause of morbidity and mortality worldwide and have a detrimental impact on global healthcare and socio-economic development. The discovery of novel antiviral treatments has gained tremendous attention and support with the rising number of viral outbreaks. In this work, carbonaceous materials, including graphene nanoplatelets and graphene oxide nanosheets, were investigated for antiviral properties. The materials were characterized using scanning electron microscopy and transmission electron microscopy. Analysis showed the materials to be two-dimensional with lateral dimensions ranging between 1 and 4 µm for graphene oxide and 110 ± 0.11 nm for graphene nanoplatelets. Antiviral properties were assessed against a DNA virus model microorganism at concentrations of 0.5, 1.0 and 2.0 wt/v%. Both carbonaceous nanomaterials exhibited potent antiviral properties and gave rise to a viral reduction of 100% across all concentrations tested. Graphene oxide nanosheets were then incorporated into polymeric fibres, and their antiviral behaviour was examined after 3 and 24 hr. A viral reduction of 39% was observed after 24 hr of exposure. The research presented here showcases, for the first time, the antiviral potential of several carbonaceous nanomaterials, also included in a carrier polymer. These outcomes can be translated and implemented in many fields and devices to prevent viral spread and infection.

Microstructure and antibacterial efficacy of graphene oxide nanocomposite fibres.

Antibacterial polymer nanocomposite fibre meshes containing graphene oxide (GO) nanosheets were successfully prepared by pressurised gyration. The morphological and chemical composition of the resulting fibre meshes were determined using Scanning Electron Microscopy (SEM), Raman spectroscopy, Raman mapping and Fourier-Transform Infrared Spectroscopy (FT-IR). SEM showed the fibres to have an average diameter increasing from ~1-4 µm as the GO loading increased. FT-IR and Raman spectroscopy confirmed the inclusion of GO nanosheets on the fibre surface. The antibacterial potential of GO nanocomposite fibres were investigated using Escherichia coli K12. Average bacterial reduction ranged from 46 to 85 % with results favouring the strongest bioactivities of the nanocomposite containing 8 wt% of GO. Finally, bacterial toxicity of the nanocomposites was evaluated by reactive oxygen species (ROS) formation. A mechanism for the antibacterial behaviour of the nanocomposite fibres is presented. Stimulated Raman scattering imaging and spectra of the fibres post antibacterial studies showed flakes of GO distributed across the surface of the poly(methyl 2-methylpropenoate) (PMMA) fibres, which contribute to the high killing efficacy of the composites towards E. coli. GO nanosheets embedded in a polymer matrix have demonstrated the ability to retain their antibacterial properties, thus offering themselves as a promising antibacterial agent.

Superparamagnetic graphene quantum dot as a dual-modality contrast agent for confocal fluorescence microscopy and magnetomotive optical coherence tomography.

A magnetic graphene quantum dot (MGQD) nanoparticle, synthesized by hydrothermally reducing and cutting graphene oxide-iron oxide sheet, was demonstrated to possess the capabilities of simultaneous confocal fluorescence and magnetomotive optical coherence tomography (MMOCT) imaging. This MGQD shows low toxicity, significant tunable blue fluorescence and superparamagnetism, which can thus be used as a dual-modality contrast agent for confocal fluorescence microscopy (CFM) and MMOCT. The feasibility of applying MGQD as a tracer of cells is shown by imaging and visualizing MGQD labeled cells using CFM and our in-house MMOCT. Since MMOCT and CFM can offer anatomical structure and intracellular details, respectively, the MGQD for cell tracking could provide a more comprehensive diagnosis.

Tough, resilient and pH-sensitive interpenetrating polyacrylamide/alginate/montmorillonite nanocomposite hydrogels.

Alginate, a naturally abundant and environmentally friendly carbohydrate polymer, can form ionically crosslinked hydrogels with Ca2+. Therefore, a novel design of interpenetrating nanocomposite hydrogels (PMACa) is proposed, which is synthesized by in situ polymerization of acrylamide in the presence of montmorillonite platelets and sodium alginate at an elevated temperature, followed by secondary crosslinking of the hydrogel using a CaCl2 solution. PMACa displays superior tensile strength and strain at break under the fully swollen state, as well as rapid shape recovery and insignificant residual strain upon the release of an external load. Furthermore, PMACa also shows remarkable reversible pH-dependent swelling/deswelling behaviors due to the pH-sensitivities of alginate network and montmorillonite platelets. These new high-performance interpenetrating alginate-containing nanocomposite hydrogels may find potential applications as aquatic load-bearing materials for artificial tissues, actuators, agriculture, etc.

Multifunctional chitosan-magnetic graphene quantum dot nanocomposites for the release of therapeutics from detachable and non-detachable biodegradable microneedle arrays.

Biodegradable chitosan-magnetic graphene quantum dot (MGQD) nanocomposites were prepared and investigated for the release of small and large molecular weight (MWt) therapeutics from detachable and non-detachable biodegradable microneedle arrays. The presence of MGQDs in chitosan increased the electrical conductivity and biodegradation rate of chitosan while maintaining its mechanical properties. The detachable microneedle arrays were created by including a water-soluble ring of poly(ethylene glycol) (PEG) at the base of the microneedle, which enabled the rapid detachment of the microneedle shaft from the base. The PEG ring did not impede the microneedle array performance, with mechanical properties and a drug release profile of low MWt lidocaine hydrochloride similar to microneedle arrays without the ring. Without the PEG ring, the chitosan-MGQD microneedles were electrically conductive and allowed for electrically stimulated release of large MWt therapeutics which was challenging without the stimulation. These results demonstrate that chitosan nanocomposites containing MGQDs with intrinsic photoluminescent and supermagnetic properties are promising materials for developing multifunctional microneedles for targeted and tracked transdermal drug delivery.

Facile Fabrication of Porous Conductive Thermoplastic Polyurethane Nanocomposite Films via Solution Casting.

Porous conductive polymers are one of important materials, featuring lightweight, large specific surface area and high porosity. Non-solvent induced phase separation is widely employed to prepare porous polymer sheet materials. Through utilizing water vapor in ambient environment as the non-solvent, a facile approach was developed to produce porous conductive polymer nanocomposites using the conventional solution-casting method. Without using any non-solvent liquids, porous carbon nanofiber/thermoplastic polyurethane (CNF/TPU) nanocomposites were prepared directly by solution casting of their dimethylformamide (DMF) solutions under ambient conditions. The strength of the CNF framework played a key role in preventing the collapse of pores during DMF evaporation. The dependence of porous structures on CNF loading was studied by scanning electron microscopy and porosity measurement. The influence of CNF loading on the mechanical properties, electrical conductivity and piezoresistive behavior was explored.

Synthesis and mechanical properties of double cross-linked gelatin-graphene oxide hydrogels.

Gelatin is an interesting biological macromolecule for biomedical applications. Here, double cross-linked gelatin nanocomposite hydrogels with incorporation of graphene oxide (GO) were synthesized in one pot using glutaraldehyde (GTA) and GTA-grafted GO as double chemical cross-linkers. The nanocomposite hydrogels, in contrast to the neat gelatin hydrogel, exhibited significant increases in mechanical properties by up to 288% in compressive strength, 195% in compressive modulus, 267% in compressive fracture energy and 160% shear storage modulus with the optimal GO concentration. Fourier transform infrared spectroscopy, scanning electron microscopy and swelling tests were implemented to characterize the nanocomposite hydrogels.

Highly Stretchable and Highly Resilient Polymer-Clay Nanocomposite Hydrogels with Low Hysteresis.

Highly stretchable and highly resilient polymer-clay nanocomposite hydrogels were synthesized by in situ polymerization of acrylamide in the presence of pristine montmorillonite (MMT) or chitosan-treated MMT nanoplatelets at an elevated temperature. Both nanocomposite hydrogels can be stretched to a strain of no less than 1290%. The treatment of clay with chitosan improves the tensile strength, elongation at break, and energy at break of the nanocomposite hydrogel by 237%, 102%, and 389%, respectively, due to the strong chitosan-MMT electrostatic interaction and the grafting of polyacrylamide onto chitosan chains. Both hydrogels display excellent resilience with low hysteresis; with a maximum tensile strain of 50%, ultralow hysteresis is found, while, with a maximum strain of 500%, both hydrogels fully recover their original state in just 1 min. The superb resilience of the nanocomposite hydrogels is attributed to the strong interactions within the hydrogels brought by chain branching, multiple hydrogen bonding, covalent bonding, and/or electrostatic force. The hydrogels can be fabricated into different shapes and forms, including microfibers spun using pressurized gyration, which may find a variety of potential applications in particular in healthcare.