Treatment of neovascular age-related macular degeneration: insights into drug-switch real-world from the Berlin Macular Registry.

PURPOSE: Bevacizumab, ranibizumab, and aflibercept are commonly used to treat neovascular age-related macular degeneration (nAMD). The results of various interventional, mostly randomized head-to-head studies, indicate statistical non-inferiority of these three drugs. The results of these studies are often interpreted as the three drugs being freely interchangeable, resulting in some health systems to pressure ophthalmologists to preferentially use the less expensive bevacizumab. This study analyzes switching from aflibercept or ranibizumab to bevacizumab and back under real-world conditions in order to investigate the assumption of interchangeability of the drugs. METHODS: Treatment data of IVT patients with diagnosed nAMD were extracted from the clinical Berlin Macular Registry database. Patients who underwent a drug switch from aflibercept or ranibizumab to bevacizumab were subject of this study. Statistical comparisons were pre-planned for best corrected visual acuity, central retinal thickness, macular volume, and length of injection interval. Additional endpoints were analyzed descriptively. RESULTS: Mean visual acuity decreased from 0.57 ± 0.05 under aflibercept/ranibizumab to 0.68 ± 0.06 logMAR after the switch (P = 0.001; N = 63). CRT increased from 308 ± 11 µm to 336 ± 16 µm (P = 0.011; N = 63). About half of the subjects were switched back: visual acuity increased from 0.69 ± 0.08 logMAR to 0.58 ± 0.09 logMAR (N = 26). CRT decreased from 396 ± 28 to 337 ± 20 µm (N = 28). CONCLUSION: The data provides real-world evidence that there is loss of visual acuity and an increase in retinal edema after switching to bevacizumab. Thus, the assumption of free interchangeability cannot be confirmed in this cohort.

Proton Therapy for 166 Patients with Iris Melanoma: Side Effects and Oncologic Outcomes.

OBJECTIVE: To investigate the oncologic and functional outcomes of a large cohort of patients with a favorable stage of circumscribed and diffuse iris melanoma who underwent primary proton treatment and the risk factors related to initial tumor characteristics and the treatment field architecture. DESIGN: Retrospective, single-center, case study. PARTICIPANTS: We reviewed 225 patients with iris melanoma who were consecutively treated with proton beam therapy at our institution between 1998 and 2020. METHODS: We performed Kaplan-Meier time-to-event analyses and multivariate Cox proportional hazard analyses to identify the impacts of tumor characteristics and target volumes on oncologic and functional outcomes. MAIN OUTCOME MEASURES: We measured local tumor control, eye preservation rates, metastasis-free survival, cataract and glaucoma-directed surgery, intraocular pressure, and changes in visual acuity. RESULTS: Of the 192 patients with tumors confined to the iris (T1a-c) who underwent proton therapy as primary treatment, a total of 166 patients (mean age, 58.4 years; 88 women) with a minimum follow-up of 6 months were included. Multifocal or diffuse tumor spread was present in 77 (46.4%) patients. The median follow-up time was 54.0 (interquartile range, 27.4-91.8 months) months. Local recurrence occurred in 2 patients (1.2%) with circumscribed iris melanoma. Enucleation was a rare event (n = 5, 3%) and no patient developed metastatic disease. A large-treatment field (full aperture, involving > 10 clock hours) was identified as a risk factor for the development of secondary glaucoma (hazard ratio [HR], 6.3; P < 0.001) and subsequent surgical interventions (HR, 10.85; P < 0.001). The large-treatment field group showed a significant decline in visual acuity (logarithm of the minimum angle of resolution > 0.3; log-rank P < 0.0001), which was associated with secondary glaucoma (HR, 3.40; P = 0.002). CONCLUSIONS: Proton therapy provides an effective, noninvasive treatment option for patients with a favorable stage of iris melanoma. Irradiation of the anterior segment for up to 10 clock hours is associated with a low risk of the development of secondary glaucoma and vision loss. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Impact of Adjuvant Ocular Interventions on the Quality of Life of Patients with Uveal Melanoma after Proton Beam Therapy.

Introduction: Proton beam therapy is an established primary treatment for patients with nonmetastasized uveal melanoma. Adjuvant local interventions, like intravitreal injections or surgery, were shown to improve long-term eye preservation; however, their impact on the patient's quality of life (QOL) remains unknown. Methods: In a post-radiotherapeutic follow-up, we prospectively collected data on QOL, visual acuity, and interventional adjuvant procedures. QOL was measured with QOL-C30 questionnaire and quality of life questionnaire OPT30 at baseline, and at 3 and 12 months after proton therapy. Patients were grouped by the type of adjuvant treatment. The impact on QOL was analyzed by comparing changes in the mean score values and visual acuity for different interventional subgroups, with generalized linear mixed models and Wilcoxon signed-rank tests. Results: We received 108 (100%) and 95 (88.0%) questionnaires at 3 and 12 months post-therapy, respectively. Adjuvant interventions included observation (n = 61, 56.5%), intravitreal injections (n = 17, 15.7%), and an intraocular surgical procedure (n = 30, 27.8%). In the latter group, several QOL items significantly declined after the 3-month adjuvant interval, but they partially recovered at the 12-month follow-up. In all adjuvant-intervention groups, global QOL scores returned to baseline levels at 12 months. Conclusion: Posttreatment adjuvant interventions had no long-lasting effects on QOL in patients with uveal melanoma.

Primary Vitreoretinal Lymphoma Therapy Monitoring: Significant Vitreous Haze Reduction After Intravitreal Rituximab.

BACKGROUND/AIMS: Intravitreal rituximab is an off-label treatment option for primary vitreoretinal lymphoma (PVRL). The objective of this study was to monitor the therapeutic response and safety profile of intravitreal rituximab in a cohort of PVRL patients. METHODS: In this retrospective, uncontrolled, open label, multicentre study, 20 eyes from 15 consecutive patients diagnosed with PRVL received at least one intravitreal injection of 1mg in 0.1ml rituximab. Biodata of the PVRL patients was recorded as well as visual acuity and vitreous haze score immediately before rituximab intravitreal injection and at follow-up examinations. Intravitreal rituximab safety data was also recorded. Additional rituximab injections were made during control visits on a pro re nata (PRN) regime using increased vitreous haze to indicate recurrence. RESULTS: There was significant vitreous haze reduction (p=0.0002) followed by significant improvement of visual acuity (mean best visual acuity before therapy 0.57 logMAR, after therapy 0.20 logMAR (p=0.0228) during the follow-up time up to 4 years. Only mild ocular side effects were reported. Median follow-up time was 565 days (range, 7-1253 days). CONCLUSION: Intravitreal rituximab therapy shows promising PVRL regression without any severe side effects. Although our clinical data support rituximab as intravitreal therapy in PVRL disease, further study is warranted.

In Situ Monitoring of Membrane Protein Insertion into Block Copolymer Vesicle Membranes and Their Spreading via Potential-Assisted Approach.

Synthosomes are polymer vesicles with transmembrane proteins incorporated into block copolymer membranes. They have been used for selective transport in or out of the vesicles as well as catalysis inside the compartments. However, both the insertion process of the membrane protein, forming nanopores, and the spreading of the vesicles on planar substrates to form solid-supported biomimetic membranes have been rarely studied yet. Herein, we address these two points and, first, shed light on the real-time monitoring of protein insertion via isothermal titration calorimetry. Second, the spreading process on different solid supports, namely, SiO2, glass, and gold, via different techniques like spin- and dip-coating as well as a completely new approach of potential-assisted spreading on gold surfaces was studied. While inhomogeneous layers occur via traditional methods, our proposed potential-assisted strategy to induce adsorption of positively charged vesicles by applying negative potential on the electrode leads to remarkable vesicle spreading and their further fusion to form more homogeneous planar copolymer films on gold. The polymer vesicles in our study are formed from amphiphilic copolymers poly(2-methyl oxazoline)-block-poly(dimethylsiloxane)-block-poly(2-methyl oxazoline) (PMOXA-b-PDMS-b-PMOXA). Engineered variants of the transmembrane protein ferric hydroxamate uptake protein component A (FhuA), one of the largest ß-barrel channel proteins, are used as model nanopores. The incorporation of FhuA Δ1-160 is shown to facilitate the vesicle spreading process further. Moreover, high accessibility of cysteine inside the channel was proven by linkage of a fluorescent dye inside the engineered variant FhuA ΔCVFtev and hence preserved functionality of the channels after spreading. The porosity and functionality of the spread synthosomes on the gold plates have been examined by studying the passive ion transport response in the presence of Li+ and ClO4- ions and electrochemical impedance spectroscopy analysis. Our approach to form solid-supported biomimetic membranes via the potential-assisted strategy could be important for the development of new (bio-) sensors and membranes.

Radiation-Induced Optic Neuropathy: Observation versus Intravitreal Treatment: Can Visual Acuity Be Maintained by Intravitreal Treatment?

PURPOSE: To compare intravitreal therapy with the natural course of radiation optic neuropathy after primary proton beam therapy for choroidal melanoma with respect to long-term visual acuity and development of optic atrophy. DESIGN: Retrospective comparative case series. METHODS: Inclusion criteria: patients treated with primary proton beam therapy for choroidal melanoma with a minimum follow-up of 24 months after the occurrence of radiation optic neuropathy and optic disc imaging during follow-up. EXCLUSION CRITERIA: pathologic condition of the optic disc before irradiation and intravitreal therapy to treat cystoid macular edema not originating from the optic disc. RESULTS: Of 93 patients, 48 were observed only after radiation optic neuropathy, and 45 were treated with intravitreal therapy (triamcinolone, bevacizumab, and/or dexamethasone). Median follow-up was 55 months (29-187 months); median interval between onset of radiation optic neuropathy and the last patient visit was 34 months (24-125 months). Of 48 observed patients, 41 (85.4%) developed an optic atrophy after a median of 14 months (3-86 months) after radiation optic neuropathy; and of 45 intravitreally treated patients, 34 (75.5%) presented with an optic atrophy after a median of 12.5 months (1-55 months) following optic neuropathy, indicating no statistically significant differences between the groups. Comparing the change in visual acuity from occurrence of optic neuropathy to final visual acuity, no statistically significant differences were found between either group (P = 0.579). CONCLUSIONS: Patients treated with intravitreal therapy for radiation optic neuropathy showed no statistically significant differences related to visual acuity or optic atrophy development from patients who underwent only observation.

[Peripheral Ischemia in Diabetic Retinopathy and Retinal Vein Occlusion: New Insights with Ultra-Wide-Angle Fundus Imaging and Wide-Angle Fluorescein Angiography]. / Periphere Ischämie bei diabetischer Retinopathie und retinalen Venenthrombosen: neue Einblicke durch die Ultraweitwinkelfundusfotografie und Weitwinkelangiografie.

BACKGROUND: In several diseases such as diabetic retinopathy and retinal vein occlusion, relevant pathophysiological changes take place in the retinal periphery. These changes may determine the prognosis and outcomes of therapy. Recent ultra-wide-angle camera systems promise improved and simplified visualisation of the outer periphery of the retina. This could potentially lead to novel clinical applications of these methods, with potential impact on therapy decisions. MATERIAL AND METHODS: Literature and database research on ultra-wide imaging for diabetic retinopathy and retinal vein occlusion. RESULTS: With ultra-wide-angle angiography, it is possible to visualise up to 3.2-fold more retinal surface than conventional 7SF images (7SF: 7 standard field). Initial studies imply that diabetic changes can be found outside of the boundaries of the 7SF images. Patients with central vein occlusion have more extended and severe macular oedema and poorer visual acuity if ischemia of the periphery is more pronounced (measured by the ischemic index [ISI]). The amount of ischemia influences the size of the macular oedema, its resolution under therapy and the number of anti-VEGF injections needed to treat it. DISCUSSION: Ultra-wide-angle camera systems allow visualisation of the peripheral retina outside the boundaries of standard methods. Initial studies have detected potentially relevant changes in the outer periphery, which would have been missed by 7SF. Nevertheless, there have been no systematic studies on the relevance of these changes with regards to prognosis and therapeutic decisions.

Neoadjuvant proton beam irradiation vs. adjuvant ruthenium brachytherapy in transscleral resection of uveal melanoma.

BACKGROUND: Uveal melanoma is the most common primary ocular malignancy in adults in the USA and Europe. The optimal treatment of large uveal melanoma is still under debate. Radiation therapy has its limitation due its eye-threatening secondary complications and is therefore often combined with surgical excision of the tumor. METHODS: In a retrospective interventional review, we evaluated in total 242 patients with uveal melanoma that underwent transscleral tumor resection with a predefined protocol, either with adjuvant ruthenium brachytherapy (Ru-106 group, n 136,), or with neoadjuvant proton beam therapy (PBT group, n 106). Kaplan-Meier estimates with log-rank test were used to show survival curves and a multivariable Cox regression model was used to calculate adjusted rate ratios. RESULTS: Local tumor recurrence rates after 3 and 5 years were 4% (95% CI 1.2-17.8%) and 9.1% (95% CI 2.9-27.3%), respectively, in the PBT group and 24.6% (95% CI 15.8-37.1%) and 27.5 (95% CI 17.8-41.1%), respectively, in the Ru-106 group. This leads to an overall recurrence rate almost 4 times higher in the Ru-106 group compared to the PBT group. After adjusting for the a priori confounders and the tumor distance to optic disc and ciliary body infiltration, the adjusted risk of tumor recurrence was 8 times (RR 7.69 (2.22-26.06), p < 0.001) higher in the Ru-106 group as compared to the PBT group. Three- and 5-year metastatic rates were 23.2% (95% CI 5.6-37.1%) and 31.8% (95% CI 20.7-46.8%), respectively, in the PBT group and 13.2% (95% CI 6.8-24.9%) and 30.3% (95% CI 18.3-47.5%), respectively, in the Ru-106 group. There was no statistically significant difference in the overall metastasis rate between the two groups even after adjusting for possible confounders. CONCLUSION: Transscleral resection of large uveal melanomas combined with neoadjuvant proton beam therapy leads to a lower local tumor recurrence rate compared to transscleral tumor resection with adjuvant ruthenium brachytherapy. There was no statistically significant difference in the occurrence of rubeosis iridis, neovascular glaucoma, and in the need for enucleation later on.

Proton Beam Irradiation: A Safe Procedure in Postequatorial Extraocular Extension From Uveal Melanoma.

PURPOSE: This study was performed to show long-term outcomes concerning metastasis rates and local recurrence rates after primary proton beam therapy in uveal melanoma with posterior extraocular extension (EOE) with the main focus on optic nerve invasion. DESIGN: Retrospective case series. METHODS: All patients treated with primary proton beam therapy for choroidal or ciliary body melanoma with posterior EOE between July 1998 and August 2010 were included. EOE was detected either upon sonography at primary examination or during the surgical application of tantalum clips onto the sclera. Ultrasound was performed in each patient before surgery, and if EOE was detected, a magnetic resonance imaging (MRI) scan was performed to confirm EOE. All patients with tumors exceeding 6 mm in thickness or abutting the optic disc received a 1.5 Tesla MRI scan after clip surgery. To assess EOE during follow-up, either ultrasound examinations or-if initially detected only by MRI-MRI scans were performed during follow-up. RESULTS: A total of 27 patients underwent primary proton beam therapy. The EOE was separated into 3 growth types: optic nerve infiltration in 10 patients, vortex vein infiltration in 9 patients, and transscleral growth postequatorially in 8 patients. No local recurrences were found during the overall median follow-up of 80 months (11-168 months). Metastasis rates correlated with AJCC stages but not EOE volume. CONCLUSION: This study shows that posterior EOE can safely be treated by proton beam therapy, even if the optic nerve is infiltrated. MRI enables safe detection of optic nerve invasion.

Synthesis and Characterization of Methyl Cellulose/Keratin Hydrolysate Composite Membranes.

It is known that aqueous keratin hydrolysate solutions can be produced from feathers using superheated water as solvent. This method is optimized in this study by varying the time and temperature of the heat treatment in order to obtain a high solute content in the solution. With the dissolved polypeptides, films are produced using methyl cellulose as supporting material. Thereby, novel composite membranes are produced from bio-waste. It is expected that these materials exhibit both protein and polysaccharide properties. The influence of the embedded keratin hydrolysates on the methyl cellulose structure is investigated using Fourier transform infrared spectroscopy (FTIR) and wide angle X-ray diffraction (WAXD). Adsorption peaks of both components are present in the spectra of the membranes, while the X-ray analysis shows that the polypeptides are incorporated into the semi-crystalline methyl cellulose structure. This behavior significantly influences the mechanical properties of the composite films as is shown by tensile tests. Since further processing steps, e.g., crosslinking, may involve a heat treatment, thermogravimetric analysis (TGA) is applied to obtain information on the thermal stability of the composite materials.

Controlling the bio-inspired synthesis of silica.

The influence of different parameters on the silicification procedure using lysozyme is reported. When polyethoxysiloxane (PEOS), an internally crosslinked silica reservoir, is used, regular structures with a narrow size distribution could be obtained only via introducing the silica precursor in two steps including initial dropping and subsequent addition of residual oil phase in one portion. We found that mixing sequence of mineralizing agents in the presence of a positively charged surfactant plays a key role in terms of silica precipitation when tetraethoxyorthosilicate (TEOS) is the oil phase. In contrast, well-mineralized crumpled features with high specific surface area could be synthesized in the presence of PEOS as a silica precursor polymer, regardless of mixing sequence. Moreover, introducing sodium dodecyl sulfate (SDS) as a negatively charged surfactant resulted in regular silica sphere formation only in combination with hexylene glycol (MPD) as a specific co-solvent. Finally, it is demonstrated that by inclusion of different nanoparticles even more sophisticated hybrid materials can be generated.

Adsorption and rheological behavior of an amphiphilic protein at oil/water interfaces.

Hydrophobins are highly surface active proteins which self-assemble at hydrophilic-hydrophobic interfaces into amphipathic membranes. We investigate hydrophobin self-assembly at oil/water interfaces to deepen the understanding of protein behavior in order to improve our biomimetic synthesis. Therefore, we carried out pendant drop measurements of hydrophobin stabilized oil/water systems determining the time-dependent IFT and the dilatational rheology with additional adaptation to the Serrien protein model. We show that the class I hydrophobin H(∗)Protein B adsorbs at an oil/water interface where it forms a densely-packed interfacial protein layer, which dissipates energy during droplet oscillation. Furthermore, the interfacial protein layer exhibits shear thinning behavior.

Antiangiogenic or Corticosteroid Treatment in Patients With Radiation Maculopathy After Proton Beam Therapy for Uveal Melanoma.

PURPOSE: To reveal differences or advantages in regard to different treatment options after proton beam therapy for uveal melanoma. DESIGN: Retrospective, comparative, interventional case series. METHODS: All patients receiving intravitreal treatment between January 2011 and July 2014 for radiation maculopathy after proton beam therapy were included. Excluded were all patients who required re-irradiation, vitrectomies, or tumor resections; and those whose treatment was performed for potentially other reasons, such as radiation-induced optic neuropathy, or where visual outcome was influenced by tumor growth under the macula or macular ischemia. Minimum follow-up was 12 months after last injection. RESULTS: Of 78 patients, 38 (48.7%) received bevacizumab injections, 35 (44.9%) triamcinolone acetonide injections, and 5 (6.4%) a dexamethasone implant. In the bevacizumab group visual acuity improved in 11 patients (28.9%) by 0.25 logMAR (0.1-0.4 logMAR) and remained stable in 24 patients (63.2%) 4 weeks after injection. In the triamcinolone group visual acuity showed improved outcomes in 10 patients (28.6%) by 0.25 logMAR (0.1-0.4 logMAR) and stability in function in 20 patients (57.1%). Four weeks after dexamethasone implantation visual acuity remained stable in 4 patients (80%). No differences among the groups were detected regarding functional outcome or reduction in central foveal thickness. CONCLUSIONS: This study showed that antiangiogenic or corticosteroid intravitreal treatment led to reduced central foveal thickness and visual improvement in some patients without showing differences or advantages. Therefore a patient-specific treatment choice can be recommended.

Cataract development in patients treated with proton beam therapy for uveal melanoma.

PURPOSE: To evaluate the incidence, risk factors, and dosages of proton beam therapy associated with cataract development, and long-term visual outcomes after treatment of uveal melanoma. METHODS: All patients receiving primary proton beam therapy for uveal melanoma between 1998 and 2008 with no signs of cataract before irradiation were included. A minimum follow-up of 12 months was determined. Exclusion criteria included all applied adjuvant therapies such as intravitreal injections, laser photocoagulation, tumor resections, or re-irradiation. For subgroup analysis, we included all patients who underwent brachytherapy between 1998 and 2008 for uveal melanoma, considering the above mentioned inclusion and exclusion criteria. RESULTS: Two hundred and fifty-eight patients matched our inclusion criteria. Median follow-up was 72.6 months (12.0-167.4 months). Of these 258 patients, 71 patients (66.3 %) presented with cataract after 31.3 months (0.7-142.4 months), of whom 35 (20.4 %) required surgery after 24.2 (0.7-111.1 months) to ensure funduscopic tumor control. Kaplan-Meier estimates calculated a risk for cataract of 74.3 % after 5 years. There was no increase in metastasis or local recurrence in these patients. Patient's age was the sole independent statistically significant risk factor for cataract development. The probability of cataract occurrence significantly increased with doses to lens exceeding 15-20 CGE. Neither the appearance of cataract nor cataract surgery influenced long-term visual outcome. CONCLUSION: Cataract formation is the most frequent complication after irradiation. There is no benefit vis-a-vis brachytherapy with regard to cataract development. Data indicate a dose-effect threshold of 0.5 CGE for cataractogenesis, with significantly increasing risk above a dose of 15 CGE. Furthermore, cataract surgery can be performed without an increased risk for metastasis.

Trabeculectomy in patients with uveal melanoma after proton beam therapy.

BACKGROUND: Retrospective evaluation of intraocular pressure, use of topical and systemic anti-glaucoma medication, secondary complications, local tumor control and survival in patients treated with trabeculectomy for the regulation of the intraocular pressure (IOP) after proton beam therapy for uveal melanoma. METHODS: In this retrospective clinical case series we evaluated the follow-up of 15 patients receiving a trabeculectomy as surgical treatment if the IOP could not be lowered adequately by medications or laser surgery. All patients had received proton beam therapy for uveal melanoma at the Helmholtz-Zentrum Berlin between 1998 and 2010. RESULTS: The median IOP decreased significantly from 35 mmHg ± 8.8 before TE to 16 mmHg ± 8.2 (=52.3 %) six months after TE (Wilcoxon-Mann-Whitney-U Test, p<0.01). None of the patients needed any glaucoma medication six months after trabeculectomy. Two patients developed local recurrence during follow-up, which were independent of the trabeculectomy. One patient had to be enucleated due to intractable pain and suspected remaining tumor activity. One patient died due to metastasis. CONCLUSIONS: Trabeculectomy is an option in intractable glaucoma in patients with uveal melanoma after proton beam therapy in single cases. Secondary interventions are common. Inoculation metastases are possible. Secure local tumor control must be a prerequisite for filtrating operations.

Local Recurrence After Primary Proton Beam Therapy in Uveal Melanoma: Risk Factors, Retreatment Approaches, and Outcome.

PURPOSE: To evaluate the risk factors, recurrence rates, retreatments, and long-term patient outcomes following proton beam therapy for uveal melanoma. DESIGN: Retrospective interventional case series. METHODS: All patients treated with primary proton beam therapy for uveal melanoma at the oncology service at Charité-Berlin and Helmholtz-Zentrum-Berlin between May 1998 and December 2008 were reviewed for local recurrence. Of 982 patients, 982 eyes matched the inclusion criteria. The data were obtained from electronic health records, operative reports, discharge letters, and radiation planning. Comparisons of fundus photographs and ultrasound measurements were performed to assess the growth pattern of the tumor and to determine the success of retreatment, in the case that a globe-retaining therapy was undertaken. RESULTS: Of 982 patients, 35 patients (3.6%) developed local recurrence. The median follow-up was 60.7 months (6.0-170.4 months). Local control rate was 96.4% and the overall eye retention rate was 95.0% in this cohort. Local recurrence was correlated with a higher risk for metastasis and reduced survival. Largest tumor diameter was identified as the sole statistically significant risk factor for local recurrence (P = .00001). All globe-retaining retreatment approaches for local recurrence, including proton beam therapy, brachytherapy, and transpupillary thermotherapy used for recurrences at the tumor margins, showed good local tumor control and similar metastasis-free survivals. CONCLUSIONS: This study showed that each globe-retaining retreatment approach can result in satisfying local tumor control. In case of early detection of local recurrence, preservation of the globe can be warranted. Therefore, regularly performed follow-ups should be ensured.

Glycopolymer brushes for specific lectin binding by controlled multivalent presentation of N-acetyllactosamine glycan oligomers.

A new multivalent glycopolymer platform for lectin recognition is introduced in this work by combining the controlled growth of glycopolymer brushes with highly specific glycosylation reactions. Glycopolymer brushes, synthetic polymers with pendant saccharides, are prepared by surface-initiated atom transfer radical polymerization (SI-ATRP) of 2-O-(N-acetyl-ß-d-glucosamine)ethyl methacrylate (GlcNAcEMA). Here, the fabrication of multivalent glycopolymers consisting of poly(GlcNAcEMA) is reported with additional biocatalytic elongation of the glycans directly on the silicon substrate by specific glycosylation using recombinant glycosyltransferases. The bioactivity of the surface-grafted glycans is investigated by fluorescence-linked lectin assay. Due to the multivalency of glycan ligands, the glycopolymer brushes show very selective, specific, and strong interactions with lectins. The multiarrays of the glycopolymer brushes have a large potential as a screening device to define optimal-binding environments of specific lectins or as new simplified diagnostic tools for the detection of cancer-related lectins in blood serum.

Self-assembly of tobacco mosaic virus at oil/water interfaces.

The oil/water interfacial assembly of tobacco mosaic virus (TMV) has been studied in situ by tensiometry and small-angle X-ray and neutron scattering (SAXS and SANS). TMV showed different orientations at the perfluorodecalin/water interface, depending on the initial TMV concentration in the aqueous phase. At low TMV concentration, the rods oriented parallel to the interface, mediating the interfacial interactions at the greatest extent per particle. At high TMV concentrations, the rods were oriented normal to the interface, mediating the interfacial interactions and also neutralizing inter-rod electrostatic repulsion. We found that the inter-rod repulsive forces between TMVs dominated the in-plane packing, which was strongly affected by the ionic strength and the bulk solution but not by the pH in the range of pH = 6-8.