Vitamin A-coupled stem cell-derived extracellular vesicles regulate the fibrotic cascade by targeting activated hepatic stellate cells in vivo.

Allogeneic transplantation of mesenchymal stem cell-derived extracellular vesicles (EVs) offers great potential for treating liver fibrosis. However, owing to their intrinsic surface characteristics, bare EVs are non-specifically distributed in the liver tissue after systemic administration, leading to limited therapeutic efficacy. To target activated hepatic stellate cells (HSCs), which are responsible for hepatic fibrogenesis, vitamin A-coupled small EVs (V-EVs) were prepared by incorporating vitamin A derivative into the membrane of bare EVs. No significant differences were found in the particle size and morphology between bare and V-EVs. In addition, surface engineering of EVs did not affect the expression of surface marker proteins (e.g., CD63 and CD9), as demonstrated by flow cytometry. Owing to the surface incorporation of vitamin A, V-EVs were selectively taken up by activated HSCs via receptor-mediated endocytosis. When systemically administered to mice with liver fibrosis, V-EVs effectively targeted activated HSCs in the liver tissue, resulting in reversal of the fibrotic cascade. Consequently, even at a 10-fold lower dose, V-EVs exhibited comparable anti-fibrotic effects to those of bare EVs, substantiating their therapeutic potential for liver fibrosis.

Metabolically engineered stem cell-derived exosomes to regulate macrophage heterogeneity in rheumatoid arthritis.

Despite the remarkable advances in therapeutics for rheumatoid arthritis (RA), a large number of patients still lack effective countermeasures. Recently, the reprogramming of macrophages to an immunoregulatory phenotype has emerged as a promising therapeutic strategy for RA. Here, we report metabolically engineered exosomes that have been surface-modified for the targeted reprogramming of macrophages. Qualified exosomes were readily harvested from metabolically engineered stem cells by tangential flow filtration at a high yield while maintaining their innate immunomodulatory components. When systemically administered into mice with collagen-induced arthritis, these exosomes effectively accumulated in the inflamed joints, inducing a cascade of anti-inflammatory events via macrophage phenotype regulation. The level of therapeutic efficacy obtained with bare exosomes was achievable with the engineered exosomes of 10 times less dose. On the basis of the boosted nature to reprogram the synovial microenvironment, the engineered exosomes display considerable potential to be developed as a next-generation drug for RA.

Bioorthogonally surface-edited extracellular vesicles based on metabolic glycoengineering for CD44-mediated targeting of inflammatory diseases.

Extracellular vesicles (EVs) are essential mediators in intercellular communication that have emerged as natural therapeutic nanomedicines for the treatment of intractable diseases. Their therapeutic applications, however, have been limited by unpredictable in vivo biodistribution after systemic administration. To control the in vivo fate of EVs, their surfaces should be properly edited, depending on the target site of action. Herein, based on bioorthogonal copper-free click chemistry (BCC), surface-edited EVs were prepared by using metabolically glycoengineered cells. First, the exogenous azide group was generated on the cellular surface through metabolic glycoengineering (MGE) using the precursor. Next, PEGylated hyaluronic acid, capable of binding specifically to the CD44-expressing cells, was labelled as the representative targeting moiety onto the cell surface by BCC. The surface-edited EVs effectively accumulated into the target tissues of the animal models with rheumatoid arthritis and tumour, primarily owing to prolonged circulation in the bloodstream and the active targeting mechanism. Overall, these results suggest that BCC combined with MGE is highly useful as a simple and safe approach for the surface modification of EVs to modulate their in vivo fate.

Physical properties and characterization of biodegradable films using nano-sized TiO2/poly(acrylamide-co-methyl methacrylate) composite.

In this study, biodegradable films were prepared by using corn starch, PVA, nano-sized poly(acrylamide-co-methyl methacrylate) (PAAm-co-MMA), nano-sized TiO2(P-25)/PAAm-co-MMA composite, and additives which are harmless to the human body, that is, glycerol (GL) and citric acid (CA). Nano-sized PAAm-co-MMA was synthesized by the method of emulsion polymerization. Also, nano-sized TiO2/PAAm-co-MMA composites were synthesized by wet milling for 48 h. The morphology and crystallinty of nano-sized PAAm-co-MMA and TiO2/PAAm-co-MMA composite was observed by the SEM and XRD. The physical properties such as tensile strength (TS), elongation at break (%E), degree of swelling (DS), and solubility (S) of biodegradable films were investigated. The photocatalytic degradability of starch/PVA/nano-sized TiO2/PAAm-co-MMA composite blended films was evaluated using methylene blue as photodegradation target.

Synthesis of carbon containing TiO2 nano powders by aerosol flame deposition for photocatalyst.

In-situ carbon-doped-TiO2 nano-powder was prepared by an AFD (aerosol flame deposition) technique using ethanol and isopropanol, and the photocatalytic activity of the prepared powder was examined. There were no significant effect of the solvents on the phase of the prepared TiO2, but the level of carbon in the deposits prepared with ethanol was lower than that prepared with isopropanol. Also, the average sizes of the particles prepared with ethanol were slightly smaller than that formed with isopropanol. All the samples showed excellent photocatalytic activity in the decomposing of methylene blue (MB). We even observed photocatalytic activity of the powder under visible light irradiation, although the decomposition rate of MB under this irradiation was slightly slower than under UV-A light irradiation.

Preparation of antimony films by cyclic pulsed chemical vapor deposition.

Cyclic-pulsed plasma-enhanced chemical vapor deposition (PECVD) for the formation of antimony (Sb) thin films was investigated using Sb(i-C3H7)3 and H2 plasma at temperatures of 200-275 degrees C. The effects of deposition temperature on the film properties, such as resistivity, surface roughness, and crystallinity were examined. The film growth rate (thickness/cycle) was found to be in the range of 0.10-0.5 nm/cycle. High substrate temperatures tended to promote low resistivity, high purity, and smooth surface morphology of the films, compared to low substrate temperatures. All of the deposited films were polycrystalline, with higher deposition temperatures yielding a higher crystallinity in the Sb films.