Browsing by Author "Moreno, Silvia"
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- ItemThe chemistry of cross-linked polymeric vesicles and their functionalization towards biocatalytic nanoreactors(Berlin ; Heidelberg : Springer, 2020) Moreno, Silvia; Voit, Brigitte; Gaitzsch, JensSelf-assembly of amphiphilic block copolymers into polymersomes continues to be a hot topic in modern research on biomimetics. Their well-known and valued mechanical strength can be increased even further if they are cross-linked. These additional bonds prevent a collapse or disassembly of the polymersomes and open the way towards smart nanoreactors. A variety of chemistries have been applied to obtain the desired cross-linked polymersomes, and therefore, the chemical approaches performed over time will be highlighted in this mini-review. Due to the large number of studies, a selected set of photo-cross-linked and pH-sensitive polymersomes will be specifically highlighted. This system has proven to be a very potent candidate for the formation of nanoreactors and drug delivery systems, and even for the formation of functional multicompartment cell mimics. [Figure not available: see fulltext.]. © 2020, The Author(s).
- ItemConstruction of Eukaryotic Cell Biomimetics: Hierarchical Polymersomes-in-Proteinosome Multicompartment with Enzymatic Reactions Modulated Protein Transportation(Weinheim : Wiley-VCH, 2021) Wen, Ping; Wang, Xueyi; Moreno, Silvia; Boye, Susanne; Voigt, Dagmar; Voit, Brigitte; Huang, Xin; Appelhans, DietmarThe eukaryotic cell is a smart compartment containing an outer permeable membrane, a cytoskeleton, and functional organelles, presenting part structures for life. The integration of membrane-containing artificial organelles (=polymersomes) into a large microcompartment is a key step towards the establishment of exquisite cellular biomimetics with different membrane properties. Herein, an efficient way to construct a hierarchical multicompartment composed of a hydrogel-filled proteinosome hybrid structure with an outer homogeneous membrane, a smart cytoskeleton-like scaffold, and polymersomes is designed. Specially, this hybrid structure creates a micro-environment for pH-responsive polymersomes to execute a desired substance transport upon response to biological stimuli. Within the dynamic pH-stable skeleton of the protein hydrogels, polymersomes with loaded PEGylated insulin biomacromolecules demonstrate a pH-responsive reversible swelling-deswelling and a desirable, on-demand cargo release which is induced by the enzymatic oxidation of glucose to gluconic acid. This stimulus responsive behavior is realized by tunable on/off states through protonation of the polymersomes membrane under the enzymatic reaction of glucose oxidase, integrated in the skeleton of protein hydrogels. The integration of polymersomes-based hybrid structure into the proteinosome compartment and the stimuli-response on enzyme reactions fulfills the requirements of eukaryotic cell biomimetics in complex architectures and allows mimicking cellular transportation processes.
- ItemLight-Driven Proton Transfer for Cyclic and Temporal Switching of Enzymatic Nanoreactors(Weinheim : Wiley-VCH, 2020) Moreno, Silvia; Sharan, Priyanka; Engelke, Johanna; Gumz, Hannes; Boye, Susanne; Oertel, Ulrich; Wang, Peng; Banerjee, Susanta; Klajn, Rafal; Voit, Brigitte; Lederer, Albena; Appelhans, DietmarTemporal activation of biological processes by visible light and subsequent return to an inactive state in the absence of light is an essential characteristic of photoreceptor cells. Inspired by these phenomena, light-responsive materials are very attractive due to the high spatiotemporal control of light irradiation, with light being able to precisely orchestrate processes repeatedly over many cycles. Herein, it is reported that light-driven proton transfer triggered by a merocyanine-based photoacid can be used to modulate the permeability of pH-responsive polymersomes through cyclic, temporally controlled protonation and deprotonation of the polymersome membrane. The membranes can undergo repeated light-driven swelling-contraction cycles without losing functional effectiveness. When applied to enzyme loaded-nanoreactors, this membrane responsiveness is used for the reversible control of enzymatic reactions. This combination of the merocyanine-based photoacid and pH-switchable nanoreactors results in rapidly responding and versatile supramolecular systems successfully used to switch enzymatic reactions ON and OFF on demand.
- ItemMatrix metalloproteinase-1 decorated polymersomes, a surface-active extracellular matrix therapeutic, potentiates collagen degradation and attenuates early liver fibrosis(New York, NY [u.a.] : Elsevier, 2021) Geervliet, Eline; Moreno, Silvia; Baiamonte, Luca; Booijink, Richell; Boye, Susanne; Wang, Peng; Voit, Brigitte; Lederer, Albena; Appelhans, Dietmar; Bansal, RuchiLiver fibrosis affects millions of people worldwide and is rising vastly over the past decades. With no viable therapies available, liver transplantation is the only curative treatment for advanced diseased patients. Excessive accumulation of aberrant extracellular matrix (ECM) proteins, mostly collagens, produced by activated hepatic stellate cells (HSCs), is a hallmark of liver fibrosis. Several studies have suggested an inverse correlation between collagen-I degrading matrix metalloproteinase-1 (MMP-1) serum levels and liver fibrosis progression highlighting reduced MMP-1 levels are associated with poor disease prognosis in patients with liver fibrosis. We hypothesized that delivery of MMP-1 might potentiate collagen degradation and attenuate fibrosis development. In this study, we report a novel approach for the delivery of MMP-1 using MMP-1 decorated polymersomes (MMPsomes), as a surface-active vesicle-based ECM therapeutic, for the treatment of liver fibrosis. The storage-stable and enzymatically active MMPsomes were fabricated by a post-loading of Psomes with MMP-1. MMPsomes were extensively characterized for the physicochemical properties, MMP-1 surface localization, stability, enzymatic activity, and biological effects. Dose-dependent effects of MMP-1, and effects of MMPsomes versus MMP-1, empty polymersomes (Psomes) and MMP-1 + Psomes on gene and protein expression of collagen-I, MMP-1/TIMP-1 ratio, migration and cell viability were examined in TGFβ-activated human HSCs. Finally, the therapeutic effects of MMPsomes, compared to MMP-1, were evaluated in vivo in carbon-tetrachloride (CCl4)-induced early liver fibrosis mouse model. MMPsomes exhibited favorable physicochemical properties, MMP-1 surface localization and improved therapeutic efficacy in TGFβ-activated human HSCs in vitro. In CCl4-induced early liver fibrosis mouse model, MMPsomes inhibited intra-hepatic collagen-I (ECM marker, indicating early liver fibrosis) and F4/80 (marker for macrophages, indicating liver inflammation) expression. In conclusion, our results demonstrate an innovative approach of MMP-1 delivery, using surface-decorated MMPsomes, for alleviating liver fibrosis.
- ItemMultivalent Protein-Loaded pH-Stable Polymersomes: First Step toward Protein Targeted Therapeutics(Weinheim : Wiley-VCH, 2021) Moreno, Silvia; Boye, Susanne; Ajeilat, Hane George Al; Michen, Susanne; Tietze, Stefanie; Voit, Brigitte; Lederer, Albena; Temme, Achim; Appelhans, DietmarSynthetic platforms for mimicking artificial organelles or for designing multivalent protein therapeutics for targeting cell surface, extracellular matrix, and tissues are in the focus of this study. Furthermore, the availability of a multi-functionalized and stimuli-responsive carrier system is required that can be used for sequential in situ and/or post loading of different proteins combined with post-functionalization steps. Until now, polymersomes exhibit excellent key characteristics to fulfill those requirements, which allow specific transport of proteins and the integration of proteins in different locations of polymeric vesicles. Herein, different approaches to fabricate multivalent protein-loaded, pH-responsive, and pH-stable polymersomes are shown, where a combination of therapeutic action and targeting can be achieved, by first choosing two model proteins such as human serum albumin and avidin. Validation of the molecular parameters of the multivalent biohybrids is performed by dynamic light scattering, cryo-TEM, fluorescence spectroscopy, and asymmetrical flow-field flow fractionation combined with light scattering techniques. To demonstrate targeting functions of protein-loaded polymersomes, avidin post-functionalized polymersomes are used for the molecular recognition of biotinylated cell surface receptors. These versatile protein-loaded polymersomes present new opportunities for designing sophisticated biomolecular nanoobjects in the field of (extracellular matrix) protein therapeutics.
- ItemReconstitution properties of biologically active polymersomes after cryogenic freezing and a freeze-drying process(London : RSC Publishing, 2018) Ccorahua, Robert; Moreno, Silvia; Gumz, Hannes; Sahre, Karin; Voit, Brigitte; Appelhans, DietmarReconstitution of biologically active polymersomes from the frozen or solid state into any fluid state is still a challenging issue for the design of new biological experiments and for the formulation of therapeutic agents. To gain knowledge about the reconstitution of pH-responsive and photo-crosslinked polymersomes, surface-functionalized and enzyme-containing polymersomers were cryogenically frozen (-20 °C) or freeze-dried with inulin as the lyoprotectant (0.1% w/v) and stored for a defined time period. Reconstituting those polymersomes in solution by thawing or a re-dispersing process revealed their original physical properties as well as their function as a pH-switchable enzymatic nanoreactor.