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Schmidt, John,Lee, Min Kyung,Ko, Eunkyung,Jeong, Jae Hyun,DiPietro, Luisa A.,Kong, Hyunjoon American Chemical Society 2016 Molecular pharmaceutics Vol.13 No.7
<P>Ever since proangiogenic growth factors have been used as a vascular medicine to treat tissue ischemia, efforts have been increasingly made to develop a method to enhance efficacy of growth factors in recreating microvascular networks, especially at low dose. To this end, we hypothesized that polysaccharides substituted with sulfate groups would amplify growth factor receptor activation and stimulate phenotypic activities of endothelial cells involved in neovascularization. We examined this hypothesis by modifying alginate with a controlled number of sulfates and using it to derive a complex with vascular endothelial growth factor (VEGF), as confirmed with fluorescence resonance energy transfer (FRET) assay. Compared with the bare VEGF and with a mixture of VEGF and unmodified alginates, the VEGF complexed with alginate sulfates significantly reduced the dissociation rate with the VEGFR-2, elevated VEGFR-2 phosphorylation level, and increased the number of endothelial sprouts in vitro. Furthermore, the VEGF-alginate sulfate complex improved recovery of perfusion in an ischemic hindlimb of a mouse due to the increase of the capillary density. Overall, this study not only demonstrates an important cofactor of VEGF but also uncovers an underlying mechanism by which the cofactor mitigates the VEGF-induced signaling involved in the binding kinetics and activation of VEGFR We therefore believe that the results of this study will be highly useful in improving the therapeutic efficacy of various growth factors and expediting their uses in clinical treatments of wounds and tissue defects.</P>
Leong, Jiayu,Seo, Yongbeom,Chu, Sang-Hyon,Park, Cheol,Jeon, Eun Je,Cho, Seung-Woo,Yang, Yi Yan,DiPietro, Luisa A.,Kim, Dong Hyun,Kong, Hyunjoon American Chemical Society 2018 Langmuir Vol.34 No.38
<P>Hydrogen peroxide (H<SUB>2</SUB>O<SUB>2</SUB>) is an attractive chemical because of its bleaching properties in paper and pulp industry and as a disinfectant in the food, water, and medical industries. However, it is important to monitor the residual H<SUB>2</SUB>O<SUB>2</SUB> level after its usage and prevent any unintended health problems or chemical reactions. Most H<SUB>2</SUB>O<SUB>2</SUB> sensors often utilize fluorophores or electrical circuitry that requires an additional irradiation or a digital display. To this end, this study presents a 3,3′,5,5′-tetramethylbenzidine (TMB)/horseradish peroxidase (HRP)-loaded patch that alerts the presence of high H<SUB>2</SUB>O<SUB>2</SUB> levels by generating a visible blue color. We hypothesized that water-insoluble TMB immobilized within mesoporous silica particles of proper pore diameter and structure would act as a colorimetric indicator through the H<SUB>2</SUB>O<SUB>2</SUB>-mediated oxidation within a cross-linked patch. We examined this hypothesis by immobilizing TMB molecules in mesoporous silica particles with 2 and 7 nm diameter cylindrical pores as well as on nonporous silica particles. Then, we loaded these TMB-silica particles and HRP in a porous alginate patch via sequential in situ cross-linking reaction and lyophilization. In the presence of 25-5000 μM H<SUB>2</SUB>O<SUB>2</SUB>, which simulate H<SUB>2</SUB>O<SUB>2</SUB> concentrations found in residual disinfecting fluids, the patch loaded with TMB-mesoporous silica particles with 7 nm diameter pores generated a distinct blue color with varying intensities depending on the H<SUB>2</SUB>O<SUB>2</SUB> concentration. The design principles demonstrated in this study should be applicable to a broad array of sensors to be integrated into a moldable, three-dimensional matrix.</P> [FIG OMISSION]</BR>
Lee, Min Kyung,Clay, Nicholas E.,Ko, Eunkyung,Smith, Cartney E.,Chen, Lin,Cho, Nicholas,Sung, Hak-Joon,DiPietro, Luisa,Lee, Jonghwi,Kong, Hyunjoon American Chemical Society 2018 Langmuir Vol.34 No.50
<P>Superparamagnetic iron oxide nanoparticles (SPIONs) are often encapsulated into drug-carrying nano/microsized particles for simultaneous magnetic resonance (MR) imaging and treatment of diseased tissues. Unfortunately, encapsulated SPIONs may have a limited ability to modulate the <I>T</I><SUB>2</SUB>-weighted relaxation of water protons, but this insight has not been examined systematically. This study demonstrates that SPIONs immobilized on 200 nm diameter poly(lactic-<I>co</I>-glycolic acid) (PLGA) nanoparticles using Pickering emulsification present 18-fold higher relaxivity than encapsulated SPIONs and 1.5-fold higher relaxivity than free SPIONs. In contrast, the SPIONs immobilized on 10 μm diameter PLGA particles exhibit a minor increase in MR relaxivity. This interesting finding will significantly impact current efforts to synthesize and assemble advanced MR contrast agents.</P> [FIG OMISSION]</BR>