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End date: 2021 × Start date: 2021 × Publisher: Weinheim : Wiley-VCH × Subject: polymersomes × WGL Institute: IPF ×

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    Multivalent 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, Dietmar
    Synthetic 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.
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    Construction 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, Dietmar
    The 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.