Surface termination effects on Raman spectra of Ti3C2Tx MXenes: an in situ UHV analysis.

Ti3C2Tx MXenes have typically a mixed surface termination of oxygen, hydroxyl and fluorine groups (Tx). In this work, we investigate the influence of the surface termination on the vibrational properties of Ti3C2Tx by performing thermal desorption and in situ Raman spectroscopy in ultra-high-vacuum (UHV). Significant changes in the Raman spectra occur after annealing above 600 °C, correlated with the desorption of approximately 80% of the fluorine termination, as confirmed by mass spectrometry and X-ray photoemission spectra. In particular, the intense Raman mode at 203 cm-1, usually attributed to a Ti-C-layer stretching vibration, is strongly damped upon fluorine desorption, while the broad spectral features between 220 and 680 cm-1, usually attributed to surface group vibrations, are not changing significantly. We show that the Raman spectra and the change induced by fluorine desorption are well represented by the phonon density of states instead of zone-center phonon modes. Disorder-induced Raman scattering strongly contributes to the Raman spectra. Moreover, due to the metallic nature of MXenes, charge density fluctuation scattering contributes as well. We show that the two scattering mechanisms, deformation potential and charge density fluctuation, may lead to opposite interpretations concerning the symmetry of the fluorine-related mode at 203 cm-1. This study provides new insights into the interpretation of the Raman spectra of MXenes, especially regarding the relation between surface chemistry and vibrational spectroscopy.

N-Heterocyclic Olefins on a Silicon Surface.

The adsorption of N-heterocyclic olefins (NHOs) on silicon is investigated in a combined scanning tunneling microscopy, X-ray photoelectron spectroscopy, and density functional theory study. We find that both of the studied NHOs bind covalently, with ylidic character, to the silicon adatoms of the substrate and exhibit good thermal stability. The adsorption geometry strongly depends on the N-substituents: for large N-substituents, an upright adsorption geometry is favored, while a flat-lying geometry is found for the NHO with smaller wingtips. These different geometries strongly influence the quality and properties of the obtained monolayers. The upright geometry leads to the formation of ordered monolayers, whereas the flat-lying NHOs yield a mostly disordered, but denser, monolayer. The obtained monolayers both show large work function reductions, as the higher density of the flat-lying monolayer is found to compensate for the smaller vertical dipole moments. Our findings offer new prospects in the design of tailor-made ligand structures in organic electronics and optoelectronics, catalysis, and material science.

Gradient metal nanoislands as a unified surface enhanced Raman scattering and surface enhanced infrared absorption platform for analytics.

In the last few decades, the use of plasmonics in vibrational spectroscopy has expanded the scope of (bio)analytical investigations. Nevertheless, there is a demand for a combined platform that can be simultaneously efficient for Surface Enhanced Raman Scattering (SERS) and Surface Enhanced Infrared Absorption (SEIRA). Here, we present a solution on the basis of a plasmonic Ag nanoparticle layer with a thickness gradient. The optical resonance along the layer varies from the visible to the infrared range offering optimal and intermediate sites for SERS and SEIRA of the analyte molecule (mercaptobenzonitrile). Enhancement factors for the same mode were determined to be ca. 104 and 170 for SERS and SEIRA, respectively. We present a full optical and vibrational characterization and demonstrate further tunability. The platform resolves reproducibility and comparability issues by a combination of the two methods. It also offers individualized solutions for different investigation conditions, i.e. a choice between excitation wavelengths and resonant Raman molecules. The multiple applicabilities of the presented unifying substrate can contribute to the expansion of the vibrational spectroscopic field and to analytics.

Design and synthesis of a series of bioavailable fatty acid synthase (FASN) KR domain inhibitors for cancer therapy.

We designed and synthesized a new series of fatty acid synthase (FASN) inhibitors with potential utility for the treatment of cancer. Extensive SAR studies led to highly active FASN inhibitors with good cellular activity and oral bioavailability, exemplified by compound 34. Compound 34 is a potent inhibitor of human FASN (IC50 = 28 nM) that effectively inhibits proliferation of A2780 ovarian cells (IC50 = 13 nM) in lipid-reduced serum (LRS). This cellular activity can be rescued by addition of palmitate, consistent with an on-target effect. Compound 34 is also active in many other cell types, including PC3M (IC50 = 25 nM) and LnCaP-Vancouver prostate cells (IC50 = 66 nM), and is highly bioavailable (F 61%) with good exposure after oral administration. In a pharmacodynamics study in H460 lung xenograft-bearing mice, oral treatment with compound 34 results in elevated tumor levels of malonyl-CoA and decreased tumor levels of palmitate, fully consistent with the desired target engagement.

Label-free biosensors based on in situ formed and functionalized microwires in microfluidic devices.

Label-free biosensors based on in situ formed and functionalized TTF-Au wires were developed using an integrated microfluidic system. By applying different modification protocols, TTF-Au wires were successfully used for sensitive label-free detection of catecholamines and human IgG by Raman spectroscopy.

On the Role of a Conserved Tryptophan in the Chromophore Pocket of Cyanobacteriochrome.

The cyanobacteriochrome Slr1393 can be photoconverted between a red (Pr) and green absorbing form (Pg). The recently determined crystal structures of both states suggest a major movement of Trp496 from a stacking interaction with ring D of the phycocyanobilin (PCB) chromophore in Pr to a position outside the chromophore pocket in Pg. Here, we investigated the role of this amino acid during photoconversion in solution using engineered protein variants in which Trp496 was substituted by natural and non-natural amino acids. These variants and the native protein were studied by various spectroscopic techniques (UV-vis absorption, fluorescence, IR, NIR and UV resonance Raman) complemented by theoretical approaches. Trp496 is shown to affect the electronic transition of PCB and to be essential for the thermal equilibrium between Pr and an intermediate state O600. However, Trp496 is not required to stabilize the tilted orientation of ring D in Pr, and does not play a role in the secondary structure changes of Slr1393 during the Pr/Pg transition. The present results confirm the re-orientation of Trp496 upon Pr â†’ Pg conversion, but do not provide evidence of a major change in the microenvironment of this residue. Structural models indicate the penetration of water molecules into the chromophore pocket in both Pr and Pg states and thus water-Trp contacts, which can readily account for the subtle spectral changes between Pr and Pg. Thus, we conclude that reorientation of Trp496 during the Pr-to-Pg photoconversion in solution is not associated with a major change in the dielectric environment in the two states.

Ultraviolet Resonance Raman Spectra of Serum Albumins.

The ultraviolet resonance Raman (UVRR) spectra of the two proteins bovine serum albumin (BSA) and human serum albumin (HSA) in an aqueous solution are compared with the aim to distinguish between them based on their very similar amino acid composition and structure and to obtain signals from tryptophan that has only very few residues. Comparison of the protein spectra with solutions of tryptophan, tyrosine, and phenylalanine in comparative ratios as in the two proteins shows that at an excitation wavelength of 220 nm, the spectra are dominated by the strong resonant contribution from these three amino acids. While the strong enhancement of two and one single tryptophan residue in BSA and HSA, respectively, results in pronounced bands assigned to fundamental vibrations of tryptophan, its weaker overtones and combination bands do not play a major role in the spectral range above 1800 cm-1. There, the protein spectra clearly reveal the signals of overtones and combination bands of phenylalanine and tyrosine. Assignments of spectral features in the range of Raman shifts from 3800 to 5100 cm-1 to combinations comprising fundamentals and overtones of tyrosine were supported by spectra of amino acid mixtures that contain deuterated tyrosine. The information in the high-frequency region of the UVRR spectra could provide information that is complementary to near-infrared absorption spectroscopy of the proteins.

Origin of the spectral red-shift and polarization patterns of self-assembled InGaN nanostructures on GaN nanowires.

The luminescence of InxGa1-xN nanowires (NWs) is frequently reported with large red-shifts as compared to the theoretical value expected from the average In content. Both compositional fluctuations and radial built-in fields were considered accountable for this effect, depending on the size, structure, composition, and surrounding medium of the NWs. In the present work, the emission properties of InGaN/GaN NWs grown by plasma-assisted molecular beam epitaxy are investigated in a comprehensive study combining ultraviolet-Raman and photoluminescence spectroscopy (PL) on vertical arrays, polarization-dependent PL on bundles of a few NWs, scanning transmission electron microscopy, energy-dispersive X-ray spectroscopy, and calculations of the band profiles. The roles of inhomogeneous In distribution and radial fields in the context of optical emission properties are addressed. The radial built-in fields are found to be modest, with a maximum surface band bending below 350 meV. On the other hand, variations in the local In content have been observed that give rise to potential fluctuations whose impact on the emission properties is shown to prevail over band-bending effects. Two luminescence bands with large positive and moderate negative polarization ratios of ≈+80% and ≤-60%, respectively, were observed. The red-shift in the luminescence is associated with In-rich inclusions in the NWs due to thermodynamic decomposition during growth. The negative polarization anisotropy is suggested to result from spontaneously formed superlattices in the In-rich regions of the NWs. The NWs show a preferred orthogonal absorption due to the dielectric boundary conditions and highlight the extreme sensitivity of these structures towards light polarization.

pH-Dependent Flavin Adenine Dinucleotide and Nicotinamide Adenine Dinucleotide Ultraviolet Resonance Raman (UVRR) Spectra at Intracellular Concentration.

The ultraviolet resonance Raman spectra of the adenine-containing enzymatic redox cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide in aqueous solution of physiological concentration are compared with the aim of distinguishing between them and their building block adenine in potential co-occurrence in biological materials. At an excitation wavelength of 266 nm, the spectra are dominated by the strong resonant contribution from adenine; nevertheless, bands assigned to vibrational modes of the nicotinamide and the flavin unit are found to appear at similar signal strength. Comparison of spectra measured at pH 7 with data obtained pH 10 and pH 3 shows characteristic changes when pH is increased or lowered, mainly due to deprotonation of the flavin and nicotinamide moieties, and protonation of the adenine, respectively.

Spectroscopic Analysis of Rare-Earth Silicide Structures on the Si(111) Surface.

Two-dimensional rare-earth silicide layers deposited on silicon substrates have been intensively investigated in the last decade, as they can be exploited both as Ohmic contacts or as photodetectors, depending on the substrate doping. In this study, we characterize rare-earth silicide layers on the Si(111) surface by a spectroscopic analysis. In detail, we combine Raman and reflectance anisotropy spectroscopy (RAS) with first-principles calculations in the framework of the density functional theory. RAS suggests a weakly isotropic surface, and Raman spectroscopy reveals the presence of surface localized phonons. Atomistic calculations allow to assign the detected Raman peaks to phonon modes localized at the silicide layer. The good agreement between the calculations and the measurements provides a strong argument for the employed structural model.

Controlled growth of ordered monolayers of N-heterocyclic carbenes on silicon.

N-Heterocyclic carbenes (NHCs) are promising modifiers and anchors for surface functionalization and offer some advantages over thiol-based systems. Because of their strong binding affinity and high electron donation, NHCs can dramatically change the properties of the surfaces to which they are bonded. Highly ordered NHC monolayers have so far been limited to metal surfaces. Silicon, however, remains the element of choice in semiconductor devices and its modification is therefore of utmost importance for electronic industries. Here, a comprehensive study on the adsorption of NHCs on silicon is presented. We find covalently bound NHC molecules in an upright adsorption geometry and demonstrate the formation of highly ordered monolayers exhibiting good thermal stability and strong work function reductions. The structure and ordering of the monolayers is controlled by the substrate geometry and reactivity and in particular by the NHC side groups. These findings pave the way towards a tailor-made organic functionalization of silicon surfaces and, thanks to the high modularity of NHCs, new electronic and optoelectronic applications.

In situ studies on the switching behavior of ultrathin poly(acrylic acid) polyelectrolyte brushes in different aqueous environments.

The pH-dependent switching of a poly(acrylic acid) (PAA) polyelectrolyte brush was investigated in situ using infrared spectroscopic ellipsometry (IRSE). The brush was synthesized by a "grafting to" procedure on silicon substrate with a native oxide layer. The overall thickness of the PAA brush in the dry state was approximately 5 nm. Reversible switching of the polymer brush was studied at titration from pH 2 to 10 and back in steps of 1 pH unit. The switching process was observed by monitoring the characteristic vibrational bands of the carboxylic groups of the PAA molecules. Decreasing of the C=O vibrational band amplitude and arising of a COO(-) vibrational band proved the chemical changes in the molecular structure of the brushes due to changes of the pH value in the aqueous solution. Due to the strong absorption of these bands in the IR region, the switching process could be monitored clearly. Switching the brush in several cycles with increasing and decreasing pH value showed a hysteresis-like behavior. For the first time, such hysteresis is observed in titration experiments of polyelectrolyte brushes. This behavior is attributed to the complex mechanisms of the ion's mobility in the brush layer which is explained with a suggested simplifying model describing the influence of ions inside the brush layer. In addition to the IRSE measurements, X-ray standing waves (XSW), in situ visible ellipsometry, and contact angle measurements have been performed and were in good agreement with the results from IRSE. Repetition of the in situ measurement cycles proved the good reversibility of the switching process which is highly important for practical applications of polymer brushes.

Liposomal gemcitabine (GemLip)-efficient drug against hormone-refractory Du145 and PC-3 prostate cancer xenografts.

BACKGROUND: Gemcitabine (Gemc) is an efficient chemotherapeutic drug in various cancer types (e.g., pancreas) but has only limited effects on hormone-refractory prostate cancer (HRPCa). Since HRPCa cells are highly sensitive to even low doses of Gemc in vitro, the lack of clinical effects might be due to rapid degradation of Gemc by deaminases combined with impaired accumulation in tumor tissue and PCa cells. Liposomal formulation (GemLip) is expected to protect the entrapped cytotoxic substance from enzymatic degradation and furthermore augment its accumulation within tumor tissues due to an enhanced permeability of the tumor vessels. METHODS: Anti-tumoral and anti-metastatic activity of GemLip and Gemc were investigated in two luciferase-expressing, human hormone-refractory PC-3 and Du145 HRPCa xenograft models in immunodeficient mice. Tumor growth was monitored by in vivo luminescence imaging (orthotopic) or callipering (subcutaneous). Anti-metastatic effects of treatment were determined by in vitro luciferase assay of the tissues. RESULTS: Tumor growth of subcutaneous Du145 xenografts was significantly inhibited only by GemLip (8 mg/kg: P = 0.014 and 6 mg/kg: P = 0.011) but not by conventional Gemc (360 mg/kg). In contrast, growth of orthotopic PC-3 xenografts was significantly inhibited by both, GemLip (P = 0.041) and Gemc (P = 0.002). The drugs furthermore strongly reduced spleen and liver metastases in this model. CONCLUSIONS: As shown by the very low efficient concentration of GemLip, liposomal entrapment of Gemc greatly enhances its activity. GemLip has, even at very low doses, a significant anti-tumoral and anti-metastatic therapeutic effect in HRPCa xenografts in vivo and was beneficial even when the conventional Gemc failed.

Synthesis and biological evaluation of an albumin-binding prodrug of doxorubicin that is cleaved by prostate-specific antigen (PSA) in a PSA-positive orthotopic prostate carcinoma model (LNCaP).

The prostate-specific antigen (PSA) is a serine protease that is over-expressed in prostate carcinoma and represents a molecular target for selectively releasing an anticancer agent from a prodrug formulation. We have recently investigated a macromolecular prodrug strategy for improved cancer chemotherapy based on 2 features: (i) rapid and selective binding of thiol-reactive prodrugs to the cysteine-34 position of endogenous albumin after intravenous administration, and (ii) enzymatic release of the albumin-bound drug at the tumor site (Mansour et al., Cancer Res 2003, 63, 4062-4066). In this work, we describe an albumin-binding prodrug, EMC-Arg-Ser-Ser-Tyr-Tyr--Ser-Arg-DOXO [EMC: epsilon-Maleimidocaproic acid; DOXO = doxorubicin; X = amino acid] that is cleaved by PSA. Because of the incorporation of 2 arginine residues, the prodrug exhibited excellent water-solubility and was rapidly and selectively bound to endogenous albumin. Incubation studies with PSA and tumor homogenates from PSA-positive tumors (LNCaP) demonstrated that the albumin-bound form of the prodrug was efficiently cleaved by PSA at the P(1)-P' (1) scissile bond releasing the doxorubicin dipeptide H-Ser-Arg-DOXO, which was further degraded to doxorubicin as the final cleavage product. In cell culture experiments, the prodrug was approximately 100-fold less active against LNCaP cells than the free drug. In contrast, in a mouse model of human prostate cancer using luciferase transduced LNCaP cells orthotopically implanted in SCID mice, the prodrug showed enhanced antitumor efficacy when compared to doxorubicin. Doxorubicin treatment at a dose of 2 x 4 mg/kg caused significant weight loss and mortality (-25%), and did not result in a significant antitumor response at the end of the experiment. The prodrug at 3 x 12 mg/kg doxorubicin equivalents, however, was well tolerated and induced a significant reduction in tumor size of 62% (+/-25%, **p = 0.003) as well as a decrease of the metastatic burden in the lungs as detected in luciferase assays (-50%, SD +/- 115%, *p = 0.038).

Antitumoral and antiangiogenic efficacy of bisphosphonates in vitro and in a murine RENCA model.

BACKGROUND: Bisphosphonates have shown direct antitumoral activity in vitro, in vivo and even in clinical studies, but the exact mechanism for this has not yet been elucidated. In this study the antiangiogenic potency of zoledronic acid and clodronate were evaluated. MATERIALS AND METHODS: The effects of zoledronic acid and clodronate on the proliferation of endothelial cells and different tumor cells, and on the activity of protein kinases were investigated. Furthermore in vitro experiments were performed to evaluate the underlying antiangiogenic mechanism of action. Both bisphosphonates were examined in vivo at different doses and in daily subcutaneous application in a murine renal cell carcinoma model (RENCA). The antiangiogenic activity was evaluated by immunohistochemical staining (CD31) and by determination of mouse vascular endothelial growth factor (VEGF) serum concentration. RESULTS: Zoledronic acid and clodronate inhibited proliferation of endothelial cells at lower concentrations than the different tumor cell lines did. This effect was more pronounced for zoledronic acid. The activity of almost all tested kinases was inhibited by zoledronic acid, whereas clodronate showed no effect. In the RENCA model, a significant effect of zoledronic acid on the primary tumor in a bell-shaped dose response curve with the highest efficacy between 100 Bg/kg 2xd and 200 Bg/kg 1xd, was observed. The mean vessel density (MVD) was significantly reduced by both bisphosphonates at different concentrations. This is the first report on increased mouse VEGF serum concentrations in the RENCA model. CONCLUSION: The results indicate that these bisphosphonates, particularly zoledronic acid, possess antitumoral and antiangiogenic activity.

Localized Synthesis of Conductive Copper-Tetracyanoquinodimethane Nanostructures in Ultrasmall Microchambers for Nanoelectronics.

In this work, the microfluidic-assisted synthesis of copper-tetracyanoquinodimethane (Cu-TCNQ) nanostructures in an ambient environment is reported for the first time. A two-layer microfluidic device comprising parallel actuated microchambers was used for the synthesis and enabled excellent fluid handling for the continuous and multiple chemical reactions in confined ultrasmall chambers. Different precautions were applied to ensure the reduction state of copper (Cu) for the synthesis of Cu-TCNQ charge-transfer compounds. The localized synthesis of Cu and in situ transformation to Cu-TCNQ complexes in solution were achieved by applying different gas pressures in the control layer. Additionally, various diameters of the Cu-TCNQ nano/microstructures were obtained by adjusting the concentration of the precursors and reaction time. After the synthesis, platinum (Pt) microelectrode arrays, which were aligned at the microchambers, could enable the in situ measurements of the electronic properties of the synthesized nanostructures without further manipulation. The as-prepared Cu-TCNQ wire bundles showed good conductivity and a reversible hysteretic switching effect, which proved the possibility in using them to build advanced nanoelectronics.

Thin SnOx films for surface plasmon resonance enhanced ellipsometric gas sensing (SPREE).

Background: Gas sensors are very important in several fields like gas monitoring, safety and environmental applications. In this approach, a new gas sensing concept is investigated which combines the powerful adsorption probability of metal oxide conductive sensors (MOS) with an optical ellipsometric readout. This concept shows promising results to solve the problems of cross sensitivity of the MOS concept. Results: Undoped tin oxide (SnOx) and iron doped tin oxide (Fe:SnOx) thin add-on films were prepared by magnetron sputtering on the top of the actual surface plasmon resonance (SPR) sensing gold layer. The films were tested for their sensitivity to several gas species in the surface plasmon resonance enhanced (SPREE) gas measurement. It was found that the undoped tin oxide (SnOx) shows higher sensitivities to propane (C3H8) then to carbon monoxide (CO). By using Fe:SnOx, this relation is inverted. This behavior was explained by a change of the amount of binding sites for CO in the layer due to this iron doping. For hydrogen (H2) no such relation was found but the sensing ability was identical for both layer materials. This observation was related to a different sensing mechanism for H2 which is driven by the diffusion into the layer instead of adsorption on the surface. Conclusion: The gas sensing selectivity can be enhanced by tuning the properties of the thin film overcoating. A relation of the binding sites in the doped and undoped SnOx films and the gas sensing abilities for CO and C3H8 was found. This could open the path for optimized gas sensing devices with different coated SPREE sensors.

A new approach for the treatment of malignant melanoma: enhanced antitumor efficacy of an albumin-binding doxorubicin prodrug that is cleaved by matrix metalloproteinase 2.

The progression of malignant melanoma is characterized by overexpression of a number of matrix metalloproteinases (MMPs), especially MMP-2, which play a critical role in the degradation of basement membranes and the extracellular matrix. Consequently, we assessed a drug targeting strategy in which the protease activity of MMP-2 is exploited to release an anticancer agent from a macromolecular carrier, i.e., circulating albumin. For this purpose, a water-soluble maleimide derivative of doxorubicin (1) incorporating a MMP-2 specific peptide sequence (Gly-Pro-Leu-Gly-Ile-Ala-Gly-Gln) was developed that binds rapidly and selectively to the cysteine-34 position of circulating albumin. The albumin-bound form of 1 was efficiently and specifically cleaved by MMP-2 liberating a doxorubicin tetrapeptide (Ile-Ala-Gly-Gln-DOXO) and subsequently doxorubicin. In vivo, 1 was superior to the parent compound doxorubicin in the A375 human melanoma xenograft, which is characterized by a high expression of MMP-2.

PTK787/ZK 222584, a specific vascular endothelial growth factor-receptor tyrosine kinase inhibitor, affects the anatomy of the tumor vascular bed and the functional vascular properties as detected by dynamic enhanced magnetic resonance imaging.

Antiangiogenic therapy is a promising new strategy of inhibiting tumor growthand formation of metastases. Recently, a number of compounds with different effects on tumor endothelial cells have entered clinical trials and revealed the need for diagnostic methods to detect their biological activity. Dynamic enhanced magnetic resonance imaging (dyMRI) is used in most clinical trials with antiangiogenic active compounds. We evaluated this method by using PTK787/ZK 222584, a specific inhibitor of the VEGF-receptor tyrosine kinases, which showed antitumoral and antiangiogenic activity in a murine renal cell carcinoma (RENCA) model. After intrarenal application of RENCA cells, mice developed a primary tumor and metastases to the lung and abdominal lymph nodes. After daily oral therapy for 21 days with either PTK787/ZK 222584 at a dose of 50 mg/kg or vehicle, primary tumors of all animals were analyzed by dyMRI. Gadolinium-DOTA (Dotarem) was used as a contrast agent to detect vessel permeability and contrast agent extravasation, whereas intravascular iron oxide nanoparticles (Endorem) were used to detect partial tumor blood volume. Additionally, vessel density, architecture, diameter, and blood flow velocity were investigated by appropriate methods. Surprisingly, no changes in extravasation occurred under treatment with PTK787/ZK 222584 as compared with the control group, whereas a significant decrease in vessel permeability occurred. Furthermore, an increase in partial blood volume was found in the PTK787/ZK 222584-treated group, although vessel density was reduced as seen by histology. Using the corrosion cast technique, reduction in vessel density was significant but not very pronounced and predominantly attributable to the loss of microvessels only. This finding correlated with a shift to large vessel diameters in the primary tumors of PTK787/ZK 222584-treated animals and with reduction of blood flow velocity in the tumor feeding renal artery. From these findings, we conclude that the treatment with PTK787/ZK 222584 primarily reduces the number of tumor microvessels, accompanied by a hemodynamic dilation of the remaining vessels. This dilation could influence the result of dyMRI such that no change in extravasation or even an increase in partial tumor blood volume could be observed.

A single local injection of recombinant VEGF receptor 2 but not of Tie2 inhibits retinal neovascularization in the mouse.

PURPOSE: The purpose of this study was to develop pharmacological therapeutic alternatives for ischemia-induced proliferative retinopathy. METHODS: C57BL/6J mice were placed in 76% oxygen on postnatal day 7 (P7) for 5 days. On P12 recombinant, chimeric vascular endothelial growth factor (sVEGF-R2) or sTie2 was injected intravitreally in one eye. The fellow eye received a control injection. On P17, retinal wholemounts were prepared after perfusion with fluorescein-dextran to quantify the retinopathy. RESULTS: A single intravitreal injection of sVEGF-R2 reduced pathologic vascular changes significantly (p = 0.02). No significant effect was observed after intravitreal application of sTie2 (p = 0.07), although Ang-2 was upregulated in control animals without treatment as neovascularization developed and Ang-1 was constantly transcribed (ratio PCR). CONCLUSIONS: sVEGF-R2 interferes with VEGF signaling via VEGF-R2 receptor. Thus, local application of soluble receptors for angiogenic factors is a possible therapy for proliferative retinopathy. Receptors with a wide range of ligands might prove more useful for local application than those binding few or antagonistic ligands.