Preparation of Dual Functionalized Surfaces for Covalent Immobilization of BMP-6 and Adhesive Ligands for Biological Applications

The median age of our population causes osteoporosis, bone fractures and disorders, which are also caused by multiple myeloma. In the past 25 years, regenerative medicine had gained in importance, especially for regeneration and renewal of bone tissue, which consists of different cell types composed in a very complex architecture. The growth factor bone morphogenetic protein 6 (BMP-6) belongs to the transforming growth factor β (TGF- β) superfamily and it induces the differentiation of mesenchymal stem cells into mature osteoblasts in bone leading to new bone formation. Besides induction of osteogenic differentiation, BMP-6 is also known to induce cell death in multiple myeloma cells in high concentrations. However, a systemic application is not practicable, since uncontrolled diffusion causes a wide range of side-effects. Immobilization of growth factors allows local treatment of bone fractures and defects, while it prevents uncontrolled release of growth factors. Furthermore, the required amount of growth factors can be reduced tremendously. The objective of this work was the covalent immobilization of BMP-6 co-presented with clicked integrin ligands on a structured gold nanoparticle (AuNP) platform, using blockcopolymer micellar nanolithography (BCMN) developed by Prof. Spatz and co-workers, to study integrin signaling in connection with growth factor responses. BMP-6 was selectively bound to gold nanoparticles organized in a hexagonal structure on the surface allowing to control the amount and density on the surface. I showed that surface co-presentation of BMP-6 and RGD or α5β1 integrin selective ligand promotes SMAD1/5 phosphorylation and osteogenic differentiation of the standard model system C2C12, even at amounts as low as 1 ng, whereas soluble BMP-6 application is significantly less effective. Additionally, BMP-6 was immobilized on gold nanostructured polyethylene glycol diacrylamide (PEG-DA) hydrogels containing different concentrations of cRGD in order to study the influence of the stiffness on the cell signaling. Furthermore, this approach was used to investigate the effect of immobilized BMP-6 in low doses on the multiple myeloma cell line OPM-2 to induce cell death. This approach provides for the first time the successful presentation of BMP-6 in small and defined amounts on surfaces in combination with adhesive ligands. Furthermore, covalent immobilization hinders protein release while maintaining the biological activity of the growth factor

Metal–Organic Frameworks@Polymer Composites Containing Cyanines for Near-Infrared Fluorescence Imaging and Photothermal Tumor Therapy

As a noninvasive treatment method, photothermal therapy (PTT) has been widely investigated for cancer therapy. In this work, metal–organic frameworks@polymer composites (UiO-66@CyP) with bioimaging and PTT activity were prepared by introducing cyanine-containing polymer (CyP) via multicomponent Passerini reaction in the presence of Zr-based nanoscale metal–organic frameworks (UiO-66). As-prepared UiO-66@CyP not only possesses uniformed size, controllable morphology, and excellent dispersibility in aqueous media, but also indicates strong near-infrared absorption and high photothermal conversion efficiency. Due to these combined merits, UiO-66@CyP appears to be an excellent phototherapy agent for ablation of tumor cells under a low-power laser irradiation and near-infrared fluorescence imaging agent. This work might open up a new avenue to develop multifunctional composites by integrating metal–organic frameworks with carboxyl, aldehyde, and isocyano-containing materials

<i>Q</i>_s10 and <i>Q</i>_a10 of CH₄ emission from the two marsh stands in two tidal stages (before flooding and after ebbing) from 2007 to 2009.

<p>Values are represented by means of triplicates ± 1 standard error. Significant differences in <i>Q</i>_s10 or <i>Q</i>_a10 (P < 0.05) between the two tidal stages are indicated by different letters.</p

One-Pot To Synthesize Multifunctional Carbon Dots for Near Infrared Fluorescence Imaging and Photothermal Cancer Therapy

It is an emerging focus to develop a simple and straightforward strategy to synthesize multifunctional nanomedicines for cancer imaging and treatment. In this work, a new carbon dot (named CyCD) with intrinsic theranostic properties was prepared from a hydrophobic cyanine dye [2-((<i>E</i>)-2-((<i>E</i>)-2-chloro-3-((<i>E</i>)-2-(1-(2-hydroxyethyl)-3,3-dimethylindolin-2-ylidene) ethylidene)­cyclohex-1-en-1-yl)­vinyl)-1-(2-hydroxyethyl)-3,3-dimethyl-3H-indol-1-ium iodide, CyOH] and poly­(ethylene glycol) (PEG800) via a simple solvothermal process. The as-prepared CyCD is well dispersed in water media with an average diameter of 2.9 ± 0.5 nm; it possesses favorable hydrophilicity and excellent photostability. More importantly, the strong absorption and near-IR (NIR) emission within the range from 600 to 900 nm, along with preferential uptake at tumors and high photothermal conversion efficiency (η = 38.7%), facilitate CyCD to act as an ideal theranostic agent for NIR fluorescent imaging and photothermal therapy in vitro and in vivo. This work highlights theranostic CDs as an excellent candidate for efficient cancer imaging and therapy

Equations of stepwise regression analysis for CH₄ metabolism and N₂O emission with environmental factors.

<p>Equations of stepwise regression analysis for CH₄ metabolism and N₂O emission with environmental factors.</p

Interannual variations of <i>Q</i>_a10 values (solid triangle), CH₄ emission (open circle) and air temperatures (solid circle) in the two marsh stands from 2007 to 2009.

<p>Error bars represent 1 standard error of the means.</p

Vegetation and soil properties of the two marsh stands dominated by <i>P</i>. <i>australis</i> and C. malaccensis, respectively.

<p>Different letters represent a significant difference between the two stands.</p><p>Vegetation and soil properties of the two marsh stands dominated by <i>P</i>. <i>australis</i> and C. malaccensis, respectively.</p

Relationships between CH₄ emission (mg m^-2 h^-1) and soil temperature (°C) at 10 cm depth or air temperature (°C) in the two marsh stands from 2007 to 2009 as described by the exponential function (P < 0.05).

<p>Relationships between CH₄ emission (mg m^-2 h^-1) and soil temperature (°C) at 10 cm depth or air temperature (°C) in the two marsh stands from 2007 to 2009 as described by the exponential function (P < 0.05).</p

Location of the sampling sites.

<p>Location of the sampling sites.</p

Monthly mean soil temperature (°C) at 10 cm depth or air temperature (°C) in the two marsh stands from 2007 to 2009.

<p>Data of soil (air) temperature was missing in April 2007 due to instrument failure.</p