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- ItemMechanochemical activation of disulfide-based multifunctional polymers for theranostic drug release(Cambridge : RSC, 2021) Shi, Zhiyuan; Song, Qingchuan; Göstl, Robert; Herrmann, AndreasDrug delivery systems responsive to physicochemical stimuli allow spatiotemporal control over drug activity to overcome limitations of systemic drug administration. Alongside, the non-invasive real-time tracking of drug release and uptake remains challenging as pharmacophore and reporter function are rarely unified within one molecule. Here, we present an ultrasound-responsive release system based on the mechanochemically induced 5-exo-trigcyclization upon scission of disulfides bearing cargo molecules attachedviaβ-carbonate linker within the center of a water soluble polymer. In this bifunctional theranostic approach, we release one reporter molecule per drug molecule to quantitatively track drug release and distribution within the cell in real-time. We useN-butyl-4-hydroxy-1,8-naphthalimide and umbelliferone as fluorescent reporter molecules to accompany the release of camptothecin and gemcitabine as clinically employed anticancer agents. The generality of this approach paves the way for the theranostic release of a variety of probes and drugs by ultrasound. © The Royal Society of Chemistry 2020.
- ItemLiquefaction of Biopolymers: Solvent-free Liquids and Liquid Crystals from Nucleic Acids and Proteins(Washington, DC : ACS Publications, 2017) Liu, Kai; Ma, Chao; Göstl, Robert; Zhang, Lei; Herrmann, AndreasConspectusBiomacromolecules, such as nucleic acids, proteins, and virus particles, are persistent molecular entities with dimensions that exceed the range of their intermolecular forces hence undergoing degradation by thermally induced bond-scission upon heating. Consequently, for this type of molecule, the absence of a liquid phase can be regarded as a general phenomenon. However, certain advantageous properties usually associated with the liquid state of matter, such as processability, flowability, or molecular mobility, are highly sought-after features for biomacromolecules in a solvent-free environment. Here, we provide an overview over the design principles and synthetic pathways to obtain solvent-free liquids of biomacromolecular architectures approaching the topic from our own perspective of research. We will highlight the milestones in synthesis, including a recently developed general surfactant complexation method applicable to a large variety of biomacromolecules as well as other synthetic principles granting access to electrostatically complexed proteins and DNA.These synthetic pathways retain the function and structure of the biomacromolecules even under extreme, nonphysiological conditions at high temperatures in water-free melts challenging the existing paradigm on the role of hydration in structural biology. Under these conditions, the resulting complexes reveal their true potential for previously unthinkable applications. Moreover, these protocols open a pathway toward the assembly of anisotropic architectures, enabling the formation of solvent-free biomacromolecular thermotropic liquid crystals. These ordered biomaterials exhibit vastly different mechanical properties when compared to the individual building blocks. Beyond the preparative aspects, we will shine light on the unique potential applications and technologies resulting from solvent-free biomacromolecular fluids: From charge transport in dehydrated liquids to DNA electrochromism to biocatalysis in the absence of a protein hydration shell. Moreover, solvent-free biological liquids containing viruses can be used as novel storage and process media serving as a formulation technology for the delivery of highly concentrated bioactive compounds. We are confident that this new class of hybrid biomaterials will fuel further studies and applications of biomacromolecules beyond water and other solvents and in a much broader context than just the traditional physiological conditions. © 2017 American Chemical Society.
- ItemAnti-Stokes Stress Sensing: Mechanochemical Activation of Triplet-Triplet Annihilation Photon Upconversion(Weinheim : Wiley-VCH, 2019) Yildiz, Deniz; Baumann, Christoph; Mikosch, Annabel; Kuehne, Alexander J.C.; Herrmann, Andreas; Göstl, RobertThe development of methods to detect damage in macromolecular materials is of paramount importance to understand their mechanical failure and the structure–property relationships of polymers. Mechanofluorophores are useful and sensitive molecular motifs for this purpose. However, to date, tailoring of their optical properties remains challenging and correlating emission intensity to force induced material damage and the respective events on the molecular level is complicated by intrinsic limitations of fluorescence and its detection techniques. Now, this is tackled by developing the first stress-sensing motif that relies on photon upconversion. By combining the Diels–Alder adduct of a π-extended anthracene with the porphyrin-based triplet sensitizer PtOEP in polymers, triplet–triplet annihilation photon upconversion of green to blue light is mechanochemically activated in solution as well as in the solid state. © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
- ItemMulticolor Mechanofluorophores for the Quantitative Detection of Covalent Bond Scission in Polymers(Weinheim : Wiley-VCH, 2021) Baumann, Christoph; Stratigaki, Maria; Centeno, Silvia P.; Göstl, RobertThe fracture of polymer materials is a multiscale process starting with the scission of a single molecular bond advancing to a site of failure within the bulk. Quantifying the bonds broken during this process remains a big challenge yet would help to understand the distribution and dissipation of macroscopic mechanical energy. We here show the design and synthesis of fluorogenic molecular optical force probes (mechanofluorophores) covering the entire visible spectrum in both absorption and emission. Their dual fluorescent character allows to track non-broken and broken bonds in dissolved and bulk polymers by fluorescence spectroscopy and microscopy. Importantly, we develop an approach to determine the absolute number and relative fraction of intact and cleaved bonds with high local resolution. We anticipate that our mechanofluorophores in combination with our quantification methodology will allow to quantitatively describe fracture processes in materials ranging from soft hydrogels to high-performance polymers. © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
- ItemActivation of the Catalytic Activity of Thrombin for Fibrin Formation by Ultrasound(Weinheim : Wiley-VCH, 2021) Zhao, Pengkun; Huo, Shuaidong; Fan, Jilin; Chen, Junlin; Kiessling, Fabian; Boersma, Arnold J.; Göstl, Robert; Herrmann, AndreasThe regulation of enzyme activity is a method to control biological function. We report two systems enabling the ultrasound-induced activation of thrombin, which is vital for secondary hemostasis. First, we designed polyaptamers, which can specifically bind to thrombin, inhibiting its catalytic activity. With ultrasound generating inertial cavitation and therapeutic medical focused ultrasound, the interactions between polyaptamer and enzyme are cleaved, restoring the activity to catalyze the conversion of fibrinogen into fibrin. Second, we used split aptamers conjugated to the surface of gold nanoparticles (AuNPs). In the presence of thrombin, these assemble into an aptamer tertiary structure, induce AuNP aggregation, and deactivate the enzyme. By ultrasonication, the AuNP aggregates reversibly disassemble releasing and activating the enzyme. We envision that this approach will be a blueprint to control the function of other proteins by mechanical stimuli in the sonogenetics field. © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
- ItemMechanochemical Release of Non-Covalently Bound Guests from a Polymer-Decorated Supramolecular Cage(Weinheim : Wiley-VCH, 2021) Küng, Robin; Pausch, Tobias; Rasch, Dustin; Göstl, Robert; Schmidt, Bernd M.Supramolecular coordination cages show a wide range of useful properties including, but not limited to, complex molecular machine-like operations, confined space catalysis, and rich host–guest chemistries. Here we report the uptake and release of non-covalently encapsulated, pharmaceutically-active cargo from an octahedral Pd cage bearing polymer chains on each vertex. Six poly(ethylene glycol)-decorated bipyridine ligands are used to assemble an octahedral PdII6(TPT)4 cage. The supramolecular container encapsulates progesterone and ibuprofen within its hydrophobic nanocavity and is activated by shear force produced by ultrasonication in aqueous solution entailing complete cargo release upon rupture, as shown by NMR and GPC analyses. © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
- ItemMethods for Exerting and Sensing Force in Polymer Materials Using Mechanophores(Weinheim : Wiley-VCH, 2020) Stratigaki, Maria; Göstl, RobertIn recent years, polymer mechanochemistry has evolved as a methodology to provide insights into the action-reaction relationships of polymers and polymer-based materials and composites in terms of macroscopic force application (stress) and subsequent deformation (strain) through a mechanophore-assisted coupling of mechanical and chemical phenomena. The perplexity of the process, however, from the viewpoint of mechanophore activation via a molecular-scaled disruption of the structure that yields a macroscopically detectable optical signal, renders this otherwise rapidly evolving field challenging. Motivated by this, we highlight here recent advancements of polymer mechanochemistry with particular focus on the establishment of methodologies for the efficient activation and quantification of mechanophores and anticipate to aptly pinpoint unresolved matters and limitations of the respective approaches, thus highlighting possible developments. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
- ItemControlling Optical and Catalytic Activity of Genetically Engineered Proteins by Ultrasound(Weinheim : Wiley-VCH, 2021) Zhou, Yu; Huo, Shuaidong; Loznik, Mark; Göstl, Robert; Boersma, Arnold J.; Herrmann, AndreasUltrasound (US) produces cavitation-induced mechanical forces stretching and breaking polymer chains in solution. This type of polymer mechanochemistry is widely used for synthetic polymers, but not biomacromolecules, even though US is biocompatible and commonly used for medical therapy as well as in vivo imaging. The ability to control protein activity by US would thus be a major stepping-stone for these disciplines. Here, we provide the first examples of selective protein activation and deactivation by means of US. Using GFP as a model system, we engineer US sensitivity into proteins by design. The incorporation of long and highly charged domains enables the efficient transfer of force to the protein structure. We then use this principle to activate the catalytic activity of trypsin by inducing the release of its inhibitor. We expect that this concept to switch “on” and “off” protein activity by US will serve as a blueprint to remotely control other bioactive molecules. © 2020 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
- ItemFractography of poly(: N -isopropylacrylamide) hydrogel networks crosslinked with mechanofluorophores using confocal laser scanning microscopy(Cambridge : RSC Publ., 2020) Stratigaki, Maria; Baumann, Christoph; van Breemen, Lambert C.A.; Heuts, Johan P.A.; Sijbesma, Rint P.; Göstl, RobertDue to their soft and brittle nature, the mechanical characterization of polymer hydrogels is a difficult task employing traditional testing equipment. Here, we endowed poly(N-isopropyl acrylamide) (PNIPAAm) hydrogel networks with Diels-Alder adducts of π-extended anthracenes as mechanofluorophore crosslinkers. After swelling the networks with varying amounts of water and subjecting them to force, we visualized the subsequent fluorescence caused by covalent bond scission with confocal laser scanning microscopy (CLSM) and related the intensities to the macroscopic fracture mechanics and the elastic moduli recorded with traditional uniaxial compression. The sensitivity of the mechanofluorophores allowed the analysis of low levels of mechanical stress produced via a hand-induced needle-puncturing process and, thus, is an alternative to conventional force application methods. The detection and precise localization of covalent bond scission via CLSM helps elucidating the interrelationship between molecular structure and the macroscopic properties of chemically crosslinked polymeric hydrogels. We believe that this micro-scale mechanophore-assisted fractography can establish a new paradigm for the mechanical analysis of soft matter in fields covering traditional polymer and life sciences. © 2019 The Royal Society of Chemistry.
- ItemMechanoresponsive diselenide-crosslinked microgels with programmed ultrasound-triggered degradation and radical scavenging ability for protein protection(Cambridge : RSC Publishing, 2022) Kharandiuk, Tetiana; Tan, Kok Hui; Xu, Wenjing; Weitenhagen, Fabian; Braun, Susanne; Göstl, Robert; Pich, AndrijIn the context of controlled delivery and release, proteins constitute a delicate class of cargo requiring advanced delivery platforms and protection. We here show that mechanoresponsive diselenide-crosslinked microgels undergo controlled ultrasound-triggered degradation in aqueous solution for the release of proteins. Simultaneously, the proteins are protected from chemical and conformational damage by the microgels, which disintegrate to water-soluble polymer chains upon sonication. The degradation process is controlled by the amount of diselenide crosslinks, the temperature, and the sonication amplitude. We demonstrate that the ultrasound-mediated cleavage of diselenide bonds in these microgels facilitates the release and activates latent functionality preventing the oxidation and denaturation of the encapsulated proteins (cytochrome C and myoglobin) opening new application possibilities in the targeted delivery of biomacromolecules.