Nanomodulator-Mediated Restructuring of Adipose Tissue Immune Microenvironments for Antiobesity Treatment.

In obesity, the interactions between proinflammatory macrophages and adipocytes in white adipose tissues are known to play a crucial role in disease progression by providing inflammatory microenvironments. Here, we report that the functional nanoparticle-mediated modulation of crosstalk between adipocytes and macrophages can remodel adipocyte immune microenvironments. As a functional nanomodulator, we designed antivascular cell adhesion molecule (VCAM)-1 antibody-conjugated and amlexanox-loaded polydopamine nanoparticles (VAPN). Amlexanox was used as a model drug to increase energy expenditure. Compared to nanoparticles lacking antibody modification or amlexanox, VAPN showed significantly greater binding to VCAM-1-expressing adipocytes and lowered the interaction of adipocytes with macrophages. In high fat diet-fed mice, repeated subcutaneous administration of VAPN increased the populations of beige adipocytes and ameliorated inflammation in white adipose tissues. Moreover, the localized application of VAPN in vivo exerted a systemic metabolic effect and reduced metabolic disorders, including insulin tolerance and liver steatosis. These findings suggested that VAPN had potential to modulate the immune microenvironments of adipose tissues for the immunologic treatment of obesity. Although we used amlexanox as a model drug and anti-VCAM-1 antibody in VAPN, the concept of immune nanomodulators can be widely applied to the immunological treatment of obesity.

Surface-Plasmon-Resonance Amplification of FMD Detection through Dendrimer Conjugation.

The amplification of the surface plasmon resonance (SPR) sensitivity for the foot-and-mouth disease (FMD) detection was studied using Poly(amidoamine) (PAMAM) succinamic-acid dendrimers. The dendrimers were conjugated with the complementary annealed with the aptamers capable of binding specifically to FMD peptides. The tethered layer of the dendrimer-conjugated double-stranded(ds)-aptamers was formed on the SPR sensor Au surface via a thiol bond between the aptamers and Au. After the tethered layer was formed, the surface was taken out of the SPR equipment. Then, the ds-aptamers on the surface were denatured to collect the dendrimer-conjugated single-stranded(ss)-complementary. The surface with only the remaining ss-aptamers was transferred again to the equipment. Two types of the injections, the FMD peptide only and the dendrimer-conjugated ss-complementary followed by the FMD peptides, were performed on the surface. The sensitivity was increased 20 times with the conjugation of the dendrimers, but the binding rate of the peptides became more than two times slower.

RNA Nanomedicine: Delivery Strategies and Applications.

Delivery of RNA using nanomaterials has emerged as a new modality to expand therapeutic applications in biomedical research. However, the delivery of RNA presents unique challenges due to its susceptibility to degradation and the requirement for efficient intracellular delivery. The integration of nanotechnologies with RNA delivery has addressed many of these challenges. In this review, we discuss different strategies employed in the design and development of nanomaterials for RNA delivery. We also highlight recent advances in the pharmaceutical applications of RNA delivered via nanomaterials. Various nanomaterials, such as lipids, polymers, peptides, nucleic acids, and inorganic nanomaterials, have been utilized for delivering functional RNAs, including messenger RNA (mRNA), small interfering RNA, single guide RNA, and microRNA. Furthermore, the utilization of nanomaterials has expanded the applications of functional RNA as active pharmaceutical ingredients. For instance, the delivery of antigen-encoding mRNA using nanomaterials enables the transient expression of vaccine antigens, leading to immunogenicity and prevention against infectious diseases. Additionally, nanomaterial-mediated RNA delivery has been investigated for engineering cells to express exogenous functional proteins. Nanomaterials have also been employed for co-delivering single guide RNA and mRNA to facilitate gene editing of genetic diseases. Apart from the progress made in RNA medicine, we discuss the current challenges and future directions in this field.

Lysyl oxidase-responsive anchoring nanoparticles for modulation of the tumor immune microenvironment.

In the tumor microenvironment, lysyl oxidase (LOX) is known to play a key role in stabilizing the tumor extracellular matrix. Here, we designed LOX-responsive nanoparticles to interact with the collagen matrix of the tumor microenvironment. Collagen-coated and imiquimod-loaded polydopamine nanoparticles (CPN/IQ) could form crosslinked structures with the collagen matrix via LOX. In vitro, anchoring of CPN/IQ nanoparticles was observed with LOX-secreting CT26 cells, but this was blocked by a LOX inhibitor. In CT26 tumor-bearing mice, co-administration of nanoparticles plus the LOX inhibitor did not significantly alter the antitumor efficacy among nanoparticles. In the absence of the LOX inhibitor, however, a single administration of CPN/IQ could provide sustained responsiveness to near-infrared irradiation and ablation of primary tumors. In the primary tumor microenvironment, CPN/IQ lowered the Treg cell population but increased the cytotoxic CD3+CD8+ T cell population. In splenic dendritic cells, CPN/IQ treatment significantly increased the CD11c+CD86+ and CD11c+CD80+ cell populations. In a CT26 distant tumor-rechallenge model, CPN/IQ treatment increased the cytotoxic CD3+CD8+ T cell population and provided 100% survival of mice until 64 days. This study indicates the feasibility of tumor immune microenvironment modulation using LOX-responsive size-transforming nanoparticles. Although we tested the concept in a CT26 cell-derived tumor model, the concept of LOX-responsive collagen matrix- anchoring nanoparticles may be broadly applied to other tumor tissues with LOX-rich tumor microenvironments.

Quantification of food loss and waste and its percentage estimation along the food supply chain in Korea.

Recent changes and food crisis at the international level have raised the awareness of food security in Korea; however, a problem that seems more urgent than the crisis is the lack of a national strategy for food loss and waste (FLW) in Korea. Moreover, where and to what extent food waste is generated in the food supply chain (FSC) is unknown. This study aimed to quantify food waste through material flow analysis and estimate the percentage of loss and waste at each stage of the FSC. The results revealed that 34.1% of the total supply of fruits and vegetables, meat and cereals was lost and wasted in Korea in 2015. Given that the proportion of edible parts in the food supplied for human consumption usually reaches 94.9%, a considerable amount of the food must have been discarded even though they are mostly edible. Furthermore, 47.6% of the total losses and wastes occurred at the upstream stages in the FSC, which include the agricultural production and processing stages, and 52.4% occurred at the downstream stages, which included the consumption stage, that is, distribution and household stages. In particular, more fruit and vegetable FLW were generated in the upstream stages of the FSC, whereas more meat and cereal loss and waste were generated in the downstream stages. The efficiency of policy implementation can be enhanced if food waste reduction strategies involve focusing more on areas with high losses.

Binding Behavior between Transforming-Growth-Factor-Beta1 and Its Receptor Reconstituted in Biomimetic Membranes.

Transforming growth factor ß1 (TGF-ß1) is critical to cell differentiation, proliferation, and apoptosis. It is important to understand the binding affinity between TGF-ß1 and its receptors. In this study, their binding force was measured using an atomic force microscope. Significant adhesion was induced by the interaction between the TGF-ß1 immobilized on the tip and its receptor reconstituted in the bilayer. Rupture and adhesive failure occurred at a specific force around 0.4~0.5 nN. The relationship of the force to loading rate was used to estimate the displacement where the rupture occurred. The binding was also monitored in real time with surface plasmon resonance (SPR) and interpreted with kinetics to acquire the rate constant. Using the Langmuir adsorption, the SPR data were analyzed to estimate equilibrium and association constants to be approximately 107 M-1 and 106 M-1 s-1. These results indicated that the natural release of the binding seldom occurred. Furthermore, the degree of binding dissociation, confirmed by the rupture interpretation, supported that the reverse of the binding hardly happened.

Mechanical Properties of 3-Hydroxybutyric Acid-Induced Vesicles.

The vesicle mechanical behaviors were studied upon its exposure to 3-hydroxybutyric acid using an atomic force microscope (AFM). Dipalmitoylphosphatidylcholine (DPPC) and 3-hydroxybutyric acid were used to manufacture the vesicles at their desired ratio. The deflection of an AFM probe with respect to its displacement was measured after characterizing the vesicle adsorption. The movement was analyzed with the Hertzian model to understand the physical behavior of the vesicles. However, in the deflection just prior to the first penetration, the model was a good fit, and the vesicle mechanical moduli were calculated. The moduli became lower with the higher ratio of 3-hydroxybutyric acid to DPPC, but the moduli were saturated at 0.5 of the ratio. These results appear to be the basis for the function of the metabolism associated with 3-hydroxybutyric acid, i.e., anesthetization and glycemic control, on the physical properties of cell membranes.

Reversible sulfur dioxide capture by amino acids containing a single amino group at low sulfur dioxide concentrations.

SO2, an air pollutant, is harmful to human health and causes air pollution; therefore, numerous studies have focused on the development of SO2 control technologies. Although limestone- and ammonia-based absorbents have been widely used in wet desulfurization, they are difficult to regenerate and do not enable the recycling of SO2, which is a useful resource. Recently, amino acids have attracted attention as reversible SO2 absorbents because they are eco-friendly and have excellent reactivity with SO2, as well as high regeneration performance. Glycine, L-alanine, ß-alanine, 4-aminobutyric acid, 5-aminovaleric acid, and 6-aminohexanoic acid were analyzed to investigate the relationship between SO2 absorption and the amino acid molecular structure using the simulated actual flue gas (200 ppmv SO2 + 13% CO2 in N2 balance). The SO2 absorption of amino acids (with the molecular structure of glycine and alkyl chains of various lengths) improved as the alkyl chain length increased, possibly owing to a decrease in the inductive effect in the molecular structure of the amino acid. Furthermore, 13C-nuclear magnetic resonance spectroscopy was conducted to analyze the SO2 absorption reaction mechanism (including the possible generation of irreversible species), and experiments involving a number of consecutive absorption-desorption cycles were used to confirm the reusability of the amino acids. The tested amino acids exhibited higher cyclic capacities compared to those of deep eutectic solvents and ionic liquids reported in the literature, thereby exhibiting excellent potential as SO2 absorbents. Thus, this study can guide the future design and development of eco-friendly SO2 absorbents.

Nanomaterials for antigen-specific immune tolerance therapy.

Impairment of immune tolerance might cause autologous tissue damage or overactive immune response against non-pathogenic molecules. Although autoimmune disease and allergy have complicated pathologies, the current strategies have mainly focused on symptom amelioration or systemic immunosuppression which can lead to fatal adverse events. The induction of antigen-specific immune tolerance may provide therapeutic benefits to autoimmune disease and allergic response, while reducing nonspecific immune adverse responses. Diverse nanomaterials have been studied to induce antigen-specific immune tolerance therapy. This review will cover the immunological background of antigen-specific tolerance, clinical importance of antigen-specific immune tolerance, and nanomaterials designed for autoimmune and allergic diseases. As nanomaterials for modulating immune tolerances, lipid-based nanoparticles, polymeric nanoparticles, and biological carriers have been covered. Strategies to provide antigen-specific immune tolerance have been addressed. Finally, current challenges and perspectives of nanomaterials for antigen-specific immune tolerance therapy will be discussed.

Tolerogenic Nanovaccine for Prevention and Treatment of Autoimmune Encephalomyelitis.

Herein, a tolerogenic nanovaccine is developed and tested on an animal model of multiple sclerosis. The nanovaccine is constructed to deliver the self-antigen, myelin oligodendrocyte glycoprotein (MOG) peptide, and dexamethasone on an abatacept-modified polydopamine core nanoparticle (AbaLDPN-MOG). AbaLDPN-MOG can target dendritic cells and undergo endocytosis followed by trafficking to lysosomes. AbaLDPN-MOG blocks the interaction between CD80/CD86 and CD28 in antigen-presenting cells and T cells, leading to decreased interferon gamma secretion. The subcutaneous administration of AbaLDPN-MOG to mice yields significant biodistribution to lymph nodes and, in experimental-autoimmune encephalomyelitis (EAE) model mice, increases the integrity of the myelin basic sheath and minimizes the infiltration of immune cells. EAE mice are treated with AbaLDPN-MOG before or after injection of the autoantigen, MOG. Preimmunization of AbaLDPN-MOG before the injection of MOG completely blocks the development of clinical symptoms. Early treatment with AbaLDPN-MOG at three days after injection of MOG also completely blocks the development of symptoms. Notably, treatment of EAE symptom-developed mice with AbaLDPN-MOG significantly alleviates the symptoms, indicating that the nanovaccine has therapeutic effects. Although AbaLDPN is used for MOG peptide delivery in the EAE model, the concept of AbaLDPN can be widely applied for the prevention and alleviation of other autoimmune diseases.

Removal Analysis of Residual Photoresist Particles Based on Surface Topography Affected by Exposure Times of Ultraviolet and Developer Solution.

Particle removal from the surface of a substrate has been an issue in numerous fields for a long time. In semiconductor processes, for instance, the formation of clean surfaces by removing photoresist (PR) must be followed in order to create neat patterns. Although PR removal has been intensively investigated recently, little is known about how ultraviolet (UV) and developer solutions alter the PR resin (and in what manner) near the surface. While varying the exposure times of UV and developer solution, we investigated the topographic changes on the surfaces of PR resin films and particles. The measured surface properties were then correlated with the detachment force determined using films, and eventually with the residual PR particle removal percentages obtained in a microchannel. Using a positive PR and a base developer solution, we demonstrated that UV causes the surface of PR resin to become hydrophilic and wavy, whereas the developer solution produces a surface with a larger degree of roughness by swelling and partially dissolving the resin. Ultimately, the increased roughness decreased the effective contact area between PR resins, hence decreasing the detachment force and increasing the particle removal percentages. We anticipate that our findings will help understand residual particle issues, particularly on the removal mechanism of PR resins based on surface topography.

Bifunctional 1,2,4-Triazole/12-Tungstophosphoric Acid Composite Nanoparticles for Biodiesel Production.

Here, a composite nanoparticle with an acid-base bifunctional structure has been reported for the transesterification of rapeseed oil to produce biodiesel. Triazole-PWA (PWA = 12-tungstophosphoric acid) composite materials with a hexahedral structure are produced using the precipitation method, showing the average particle diameters of 200-800 nm. XPS and FT-IR analyses indicate well-defined chemical bonding of triazole moieties to the PWA. The functionalization and immobilization of PWAs are investigated due to strong interactions with triazole, which significantly improves the thermal stability and even surface area of the heteropoly acid. Furthermore, various ratios of triazole and PWAs are examined using NH3-TPD and CO2-TPD to optimize the bi-functionality of acidity and basicity. The prepared nanomaterials are evaluated during the transesterification of rapeseed oil with methanol to analyze the effect of triazole addition to PWAs according to the different ratios. Overall, the bifunctional triazole-PWA composite nanoparticles exhibit higher fatty acid methyl ester (FAME) conversions than pure PWA nanoparticles. The optimized catalyst with a triazole:PWA ratio of 6:1 exhibits the best FAME-conversion performance due to its relatively large surface area, balance of acidity, and strong basicity from the well-designed chemical nano-structure.

Lyophilization of Curcumin-Albumin Nanoplex with Sucrose as Cryoprotectant: Aqueous Reconstitution, Dissolution, Kinetic Solubility, and Physicochemical Stability.

An amorphous curcumin (CUR) and bovine serum albumin (BSA) nanoparticle complex (nanoplex) was previously developed as a promising anticancer nanotherapy. The CUR-BSA nanoplex had been characterized in its aqueous suspension form. The present work developed a dry-powder form of the CUR-BSA nanoplex by lyophilization using sucrose as a cryoprotectant. The cryoprotective activity of sucrose was examined at sucrose mass fractions of 33.33, 50.00, and 66.66% by evaluating the lyophilized nanoplex's (1) aqueous reconstitution and (2) CUR dissolution and kinetic solubility. The physicochemical stabilizing effects of sucrose upon the nanoplex's 30-day exposures to 40 °C and 75% relative humidity were examined from (i) aqueous reconstitution, (ii) CUR dissolution, (iii) CUR and BSA payloads, (iv) amorphous form stability, and (v) BSA's structural integrity. The good cryoprotective activity of sucrose was evidenced by the preserved BSA's integrity and good aqueous reconstitution, resulting in a fast CUR dissolution rate and a high kinetic solubility (≈5-9× thermodynamic solubility), similar to the nanoplex suspension. While the aqueous reconstitution, CUR dissolution, and amorphous form were minimally affected by the elevated heat and humidity exposures, the treated nanoplex exhibited a lower BSA payload (≈7-26% loss) and increased protein aggregation postexposure. The adverse effects on the BSA payload and aggregation were minimized at higher sucrose mass fractions.

Changes in Mechanical Properties of Vesicles by Mucin in Aqueous Solution.

The mechanical properties of vesicles were investigated as they were prepared, according to the ratio of mucin to dipalmitoylphosphatidylcholine (DPPC), using an atomic force microscope (AFM). After the confirmation of the vesicle adsorption on a mica surface, an AFM-tip deflection, caused by the interaction between the tip and the vesicle, was measured. The deflection showed that the tip broke through into the vesicle twice. Each break meant a tip-penetration into the upper and lower portion of the vesicle. Only the first penetration allowed the Hertzian model available to estimate the vesicle mechanical moduli. Two moduli reduced as the ratio of mucin to DPPC increased to 0.5, but the moduli were little changed above the 0.5 ratio. These results seem to be a platform for the effect of the mucin on the plasma-membrane anchoring and cellular signaling.

In vivo fate and intracellular trafficking of vaccine delivery systems.

With the pandemic of severe acute respiratory syndrome coronavirus 2, vaccine delivery systems emerged as a core technology for global public health. Given that antigen processing takes place inside the cell, the intracellular delivery and trafficking of a vaccine antigen will contribute to vaccine efficiency. Investigations focusing on the in vivo behavior and intracellular transport of vaccines have improved our understanding of the mechanisms relevant to vaccine delivery systems and facilitated the design of novel potent vaccine platforms. In this review, we cover the intracellular trafficking and in vivo fate of vaccines administered via various routes and delivery systems. To improve immune responses, researchers have used various strategies to modulate vaccine platforms and intracellular trafficking. In addition to progress in vaccine trafficking studies, the challenges and future perspectives for designing next-generation vaccines are discussed.

Benchmarking the Solubility Enhancement and Storage Stability of Amorphous Drug-Polyelectrolyte Nanoplex against Co-Amorphous Formulation of the Same Drug.

Amorphization, typically in the form of amorphous solid dispersion (ASD), represents a well-established solubility enhancement strategy for poorly soluble drugs. Recently, two amorphous drug formulations, i.e., the amorphous drug-polyelectrolyte nanoparticle complex (nanoplex) and co-amorphous system, have emerged as promising alternatives to circumvent the issues faced by ASD (i.e., large dosage requirement, high hygroscopicity). In the present work, the nanoplex was benchmarked against the co-amorphous system in terms of the preparation efficiency, drug payload, thermal stability, dissolution rate, supersaturation generation, and accelerated storage stability. Weakly acidic curcumin (CUR) and weakly basic ciprofloxacin (CIP) were used as the model poorly soluble drugs. The CUR and CIP nanoplexes were prepared using chitosan and sodium dextran sulfate as the polyelectrolytes, respectively. The co-amorphous CUR and CIP were prepared using tannic acid and tryptophan as the co-formers, respectively. The benchmarking results showed that the amorphous drug nanoplex performed as well as, if not better than, the co-amorphous system depending on the drug in question and the aspects being compared. The present work successfully established the nanoplex as an equally viable amorphous drug formulation as the more widely studied co-amorphous system to potentially serve as an alternative to ASD.

Nano-Composite Filler of Heteropolyacid-Imidazole Modified Mesoporous Silica for High Temperature PEMFC at Low Humidity.

Nano-composite filler has received attention for the application to high temperature and low humidity polymer electrolyte membrane (PEM) in fuel cell systems. Heteropolyacids (HPAs) are one of the most attractive materials because of their conductive and thermally stable properties, but have practical limitations due to their high solubility. We investigated the stabilization of HPA on imidazole modified mesoporous silica as a nano-composite filler. The role of mesoporous silica as a support for imidazole and the distribution of chemically bonded HPA on the surface were both confirmed through physical and chemical analysis. The developed nano-composite was utilized to a PEM as a proton conducting filler, cast with commercial AquivionTM solution. Changing the HPA: imidazole ratio and HPA wt%, the composite membrane of Im10/PWA6/Si-MCM-41 (PWA 10 wt%) resulted in higher proton conductivity compared to the non-modified membrane at all operation conditions, especially at high temperature (140 °C) and low relative humidity (RH 10%), with values of 0.3530 and 0.0241 S/m, respectively. A single cell test at H2/Air also showed the effect of adding the nano-composite filler at a wide range of temperatures, which outperformed a single cell with a pristine membrane even at an extremely low humidity condition.

Ectoine Effect on Mechanical Properties of Vesicles in Aqueous Solution.

The mechanical properties of the vesicles incorporated with ectoine were studied using atomic force microscope (AFM). The vesicles were prepared with dipalmitoylphosphatidylcholine (DPPC) by changing only the ratio of the ectoine to DPPC. After the vesicles were adsorbed on the mica substrate and their morphology were characterized, the plot of an AFM tip displacement versus the tip deflection was acquired by monitoring the behavior of the tip into the vesicle. The breakthrough of the tip into the vesicle was observed to occur twice. Each breakthrough represented a penetration of the tip into the top and bottom portions of the vesicle, respectively. The force data between the pre-contact and the first breakthrough were comparable with the Hertzian model to estimate Young's modulus and the bending modulus of the vesicles. Both moduli decreased proportionally with the increase in the ratio of ectoine to lipid up to 0.5. However, above 0.5, the moduli were slightly changed with the increase. These results of the mechanical properties appear to be due to the osmotic and volumetric effect on the headgroup packing disruption.

Purification of landfill gas by extracted calcium ions from municipal solid waste incineration fly ash.

This study proposes the utilization of CO2 based on the purification of landfill gas (LFG). The process included absorption of CO2 from LFG using monoethanolamine (MEA) absorbent, extraction of calcium ions from municipal solid waste incineration (MSWI) fly ash using various acids, and formation of calcium carbonate using the extracted calcium ions. During LFG purification, the concentration of CH4 in the gas after absorption was time dependent. The pH swing method was used for the extraction of calcium ions and comprised three phases: calcium ion leaching from MSWI fly ash phase, removal of cations from the supernatant, and calcium ion recovery. Hydrochloric and nitric acids, known as strong acids, and citric, acetic, and formic acids, which are weak acids, were used as extraction agents. Hydrochloric acid, nitric acid, acetic acid, and formic acid showed significant calcium ion recovery rates of 99.32%, 99.18%, 98.35%, and 97.99%, respectively, whereas citric acid showed a relatively low recovery rate of 82.82%. The extracted calcium ions were converted into calcium carbonate by reacting with ionic CO2 in the saturated MEA. The calcium carbonate formed showed different crystal structures based on the extraction agent used: aragonite for hydrochloric acid and nitric acid, amorphous CaCO3 for citric acid, vaterite for acetic acid, and calcite for formic acid. The results of this study can be applied to various CO2 utilization processes based on LFG and MSWI fly ash.