Tracking Local Mechanical Impact in Heterogeneous Polymers with Direct Optical Imaging

Structural heterogeneity defines the properties of many functional polymers and it is often crucial for their performance and ability to withstand mechanical impact. Such heterogeneity, however, poses a tremendous challenge for characterization of these materials and limits our ability to design them rationally. Herein we present a practical methodology capable of resolving the complex mechanical behavior and tracking mechanical impact in discrete phases of segmented polyurethane—a typical example of a structurally complex polymer. Using direct optical imaging of photoluminescence produced by a small‐molecule organometallic mechano‐responsive sensor we observe in real time how polymer phases dissipate energy, restructure, and breakdown upon mechanical impact. Owing to its simplicity and robustness, this method has potential in describing the evolution of complex soft‐matter systems for which global characterization techniques fall short of providing molecular‐level insight

Tracking Local Mechanical Impact in Heterogeneous Polymers with Direct Optical Imaging

Structural heterogeneity defines the properties of many functional polymers and it is often crucial for their performance and ability to withstand mechanical impact. Such heterogeneity, however, poses a tremendous challenge for characterization of these materials and limits our ability to design them rationally. Herein we present a practical methodology capable of resolving the complex mechanical behavior and tracking mechanical impact in discrete phases of segmented polyurethane—a typical example of a structurally complex polymer. Using direct optical imaging of photoluminescence produced by a small‐molecule organometallic mechano‐responsive sensor we observe in real time how polymer phases dissipate energy, restructure, and breakdown upon mechanical impact. Owing to its simplicity and robustness, this method has potential in describing the evolution of complex soft‐matter systems for which global characterization techniques fall short of providing molecular‐level insight

Elucidating dynamic behavior of synthetic supramolecular polymers in water by hydrogen/deuterium exchange mass spectrometry

A comprehensive understanding of the structure, self-assembly mechanism, and dynamics of one-dimensional supramolecular polymers in water is essential for their application as biomaterials. Although a plethora of techniques are available to study the first two properties, there is a paucity in possibilities to study dynamic exchange of monomers between supramolecular polymers in solution. We recently introduced hydrogen/deuterium exchange mass spectrometry (HDX-MS) to characterize the dynamic nature of synthetic supramolecular polymers with only a minimal perturbation of the chemical structure. To further expand the application of this powerful technique some essential experimental aspects have been reaffirmed and the technique has been applied to a diverse library of assemblies. HDX-MS is widely applicable if there are exchangeable hydrogen atoms protected from direct contact with the solvent and if the monomer concentration is sufficiently high to ensure the presence of supramolecular polymers during dilution. In addition, we demonstrate that the kinetic behavior as probed by HDX-MS is influenced by the internal order within the supramolecular polymers and by the self-assembly mechanism.MINECO, Spain, Grant/Award Number: IJCI-2015-252389; Marie Curie FP7 SASSYPOL ITN program, Grant/Award Number: 607602; European Research Council, Grant/Award Number: 788618; Dutch Ministry of Education, Culture and Science, Grant/Award Number: 024.001.03

Monitoring the Crosstalk Between the Estrogen Receptor and Human Epidermal Growth Factor Receptor 2 with PET

Purpose: Ovarian cancer (OC) leads to poor survival rates mainly due to late stage detection and innate or acquired resistance to chemotherapy. Thus, efforts have been made to exploit the estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) to treat OC. However, patients eventually become resistant to these treatments as well. HER2 overexpression contributes to the acquired resistance to ER-targeted treatment. Trastuzumab treatment, on the other hand, can result in increased expression of ER, which, in turn, increases the sensitivity of the tumors towards anti-estrogen therapy. More insight into the crosstalk between ER and HER2 signaling could improve our knowledge about acquired resistance in ovarian cancer. The aim of this study was to evaluate whether PET could be used to detect changes in ER expression induced by HER2-targeted treatment in vivo. Procedures: Male athymic nude mice were subcutaneously (sc) inoculated with 106 SKOV3 human ovarian cancer cells (HER2+/ER+). Two weeks after inoculation, tumor-bearing mice were treated intraperitoneally with either vehicle, the HER2 antibody trastuzumab (20 mg/kg, 2×/week), or the HER2-tyrosine kinase inhibitor lapatinib (40 mg/kg, 5 days/week) for 2 weeks. Thereafter, ER expression in the tumor was assessed by PET imaging with 16α-[18F]-fluoro-17β-estradiol ([18F]FES). Tumors were excised for ex vivo ER and HER2 measurement with Western blotting and immunohistochemistry. Results: All treatments led to smaller tumors than vehicle-treated tumors. Higher [18F]FES maximum standardize tumor uptake (SUVmax) was observed in animals treated with trastuzumab (+ 29 %, P = 0.002) or lapatinib (+ 20 %, P = 0.096) than in vehicle-treated controls. PET results were in agreement with ex vivo analyses. Conclusion: FES-PET imaging can detect changes in ER expression induced by HER2-targeted treatment and therefore can be used to investigate the crosstalk between ER and HER2 in a noninvasive manner

Modular Medical Imaging Agents Based on Azide-Alkyne Huisgen Cycloadditions:Synthesis and Pre-Clinical Evaluation of(18)F-Labeled PSMA-Tracers for Prostate Cancer Imaging

Since the seminal contribution of Rolf Huisgen to develop the [3+2] cycloaddition of 1,3-dipolar compounds, its azide–alkyne variant has established itself as the key step in numerous organic syntheses and bioorthogonal processes in materials science and chemical biology. In the present study, the copper(I)-catalyzed azide–alkyne cycloaddition was applied for the development of a modular molecular platform for medical imaging of the prostate-specific membrane antigen (PSMA), using positron emission tomography. This process is shown from molecular design, through synthesis automation and in vitro studies, all the way to pre-clinical in vivo evaluation of fluorine-18- labeled PSMA-targeting ‘F-PSMA-MIC’ radiotracers (t1/2=109.7 min). Pre-clinical data indicate that the modular PSMA-scaffold has similar binding affinity and imaging properties to the clinically used [68Ga]PSMA-11. Furthermore, we demonstrated that targeting the arene-binding in PSMA, facilitated through the [3+2]cycloaddition, can improve binding affinity, which was rationalized by molecular modeling. The here presented PSMA-binding scaffold potentially facilitates easy coupling to other medical imaging moieties, enabling future developments of new modular imaging agents

Supramolecular approach to new inkjet printing inks

Electronically complementary, low molecular weight polymers that self-assemble through tunable π−π stacking interactions to form extended supramolecular polymer networks have been developed for inkjet printing applications and successfully deposited using three different printing techniques. Sequential overprinting of the complementary components results in supramolecular network formation through complexation of π-electron rich pyrenyl or perylenyl chain-ends in one component with π-electron deficient naphthalene diimide residues in a chain-folding polyimide. The complementary π−π stacked polymer blends generate strongly colored materials as a result of charge-transfer absorption bands in the visible spectrum, potentially negating the need for pigments or dyes in the ink formulation. Indeed, the final color of the deposited material can be tailored by varying the end-groups of the π-electron rich polymer component. Piezoelectric printing techniques were employed in a proof of concept study to allow characterization of the materials deposited, and a thermal inkjet printer adapted with imaging software enabled in situ analysis of the ink drops as they formed and of their physical properties. Finally, continuous inkjet printing allowed greater volumes of material to be deposited, on a variety of different substrate surfaces, and demonstrated the utility and versatility of this novel type of ink for industrial applications

Side-chain supramolecular polymers employing conformer independent triple hydrogen bonding arrays

Derivatives of thymine have been extensively used to promote supramolecular materials assembly. Such derivatives can be synthetically challenging to access and may be susceptible to degradation. The current article uses a conformer-independent acceptor-donor-acceptor array (ureidopyrimidine) which forms moderate affinity interactions with diamidopyridine derivatives to effect supramolecular blend formation between polystyrene and poly(methyl methacrylate) polymers obtained by RAFT which have been functionalized with the hydrogen bonding motifs