Rapid Synthesis of Dual-Responsive Hollow Capsules with Controllable Membrane Thickness by Surface-Initiated SET-LRP Polymerization

We present a facile and highly effective route to construct a dual-responsive polymeric capsule with photo-cross-linkable property based on surface-initiated single electron transfer living radical polymerization (SI-SET-LRP) exploiting silica particles as templates, dimethyl­aminoethyl methacrylate (DMAEMA) as dual-responsive component, and 2-hydroxy-4-(methacryloyloxy)­benzophenone (BMA) as an effective photo-cross-linker. This approach is highly efficient with complete monomer conversion in 15 min at ambient temperature resulting in wall thickness of 55 nm and usable in technical applications. Hollow capsules are available after photo-cross-linking of polymeric shell and removing silica particle, of which the morphology and composition were confirmed by employing a range of techniques, such as FTIR, TGA, TEM, SEM, cryo-TEM, DLS, GPC, and UV–vis spectroscopy. Thus, it represents a significant advance in the development of complex polymeric capsules synthesis usable for various applications (e.g., biotechnology and systems biology)

Tailored Synthesis of Intelligent Polymer Nanocapsules: An Investigation of Controlled Permeability and pH-Dependent Degradability

In this study, we present a new route to synthesize an intelligent polymer nanocapsule with an ultrathin membrane based on surface-initiated reversible addition–fragmentation chain-transfer polymerization. The key concept of our report is to use pH-responsive polydiethylaminoethylmethacrylate as a main membrane-generating component and a degradable disulfide bond to cross-link the membrane. The permeability of membrane, tuned by adjusting pH and using different lengths of the cross-linkers, was proven by showing a dramatic swelling behavior of the nanocapsules with the longest cross-linker from 560 nm at pH 8.0 to 780 nm at pH 4.0. Also, due to the disulfide cross-linker, degradation of the capsules using GSH as reducing agent was achieved which is further significantly promoted at pH 4.0. Using a rather long-chain dithiol cross-linker, the synthesized nanocapsules demonstrated a good permeability allowing that an enzyme myoglobin can be postencapsulated, where the pH controlled enzyme activity by switching membrane permeability was also shown

Cellular Interactions with Photo-Cross-Linked and pH-Sensitive Polymersomes: Biocompatibility and Uptake Studies

Polymeric nanoparticles, specifically polymersomes, are at the leading edge of the rapidly developing field of nanotechnology. However, their use for biological applications is primarily limited by the biocompatibility of the components. Hence, optimization of polymersome synthesis protocols should carefully consider aspects of cellular toxicity. In this work, we investigate the viability of HDF and HeLa cells treated with photo-cross-linked and pH-sensitive polymersomes. We demonstrate how aspects of polymersome preparation conditions such as cross-linking density and UV irradiation time may affect their cytotoxic properties. Additionally, we also study the cellular uptake of our polymersomes into the cell types mentioned

Multifunctional and Dual-Responsive Polymersomes as Robust Nanocontainers: Design, Formation by Sequential Post-Conjugations, and pH-Controlled Drug Release

Robust, multiresponsive, and multifunctional nanovesicles are in high demand not only as carrier systems but also for applications in microsystem devices and nanotechnology. Hence, multifunctional, pH-responsive, and photo-cross-linked polymersomes decorated with adamantane and azide groups are prepared by mixed self-assembly of suitably end-modified block copolymers and are used for the subsequent postconjugation of the polymersome surface by using covalent and noncovalent approaches. For the covalent approach, nitroveratryloxycarbonyl-protected amine (NVOC) molecules as light-responsive moieties are introduced into the polymersomes through an azide–alkyne click reaction. After photocleavage of NVOC units, functional dye molecules react with the now freely accessible amine groups. The noncovalent approach is performed subsequently to introduce further moieties, making use of the strong adamantane-β-cyclodextrin host–guest interactions. It is quantitatively proven that all reactive groups have sufficient accessibility as well selective and orthogonal reactivity throughout these stepwise processes to allow the successful establishment of aimed pH- and light-responsive multifunctional polymersomes. Moreover, this sequential methodology is also applied to obtain doxorubicin-loaded multifunctional polymersomes for an efficient pH-controlled drug release. Overall, tunable membrane permeability combined with the potential for introducing multiple targeting groups by light-exposure or host–guest interactions make these smart polymersomes promising nanocontainers for many applications

Tetra-Sensitive Graft Copolymer Gels as Active Material of Chemomechanical Valves

Stimuli-responsive hydrogels combine sensor and actuator properties by converting an environmental stimulus into mechanical work. Those materials are highly interesting for applications as a chemomechanical valve in microsystem technologies. However, studies about key characteristics of hydrogels for this application are comparatively rare, and further research is needed to emphasize their real potential. The first part of this study depicts the synthesis of grafted hydrogels based on a poly­(<i>N</i>-isopropylacrylamide) backbone and pH-sensitive poly­(acrylic acid) graft chains. The chosen approach of grafted hydrogels provides the preparation of multiresponsive hydrogels, which retain temperature sensitivity besides being pH-responsive. A pronounced salt and solvent response is additionally achieved. Key characteristics for an application as a chemomechanical valve of the graft hydrogels are revealed: (1) independently addressable response to all stimuli, (2) significant volume change, (3) sharp transition, (4) reversible swelling–shrinking behavior, and (5) accelerated response time. To prove the concept of multiresponsive hydrogels for flow control, a <i>net</i>-poly­(<i>N</i>-acrylamide)-<i>g</i>-poly­(acrylic acid) hydrogel containing 0.6 mol % poly­(acrylic acid)-vinyl is employed as active material for chemomechanical valves. Remarkably, the chemomechanical valve can be opened and closed in a fluidic platform with four different stimuli

Immobilized Multifunctional Polymersomes on Solid Surfaces: Infrared Light-Induced Selective Photochemical Reactions, pH Responsive Behavior, and Probing Mechanical Properties under Liquid Phase

Fixing polymersomes onto surfaces is in high demand not only for the characterization with advanced microscopy techniques but also for designing specific compartments in microsystem devices in the scope of nanobiotechnology. For this purpose, this study reports the immobilization of multifunctional, responsive, and photo-cross-linked polymersomes on solid substrates by utilizing strong adamantane−β-cyclodextrin host–guest interactions. To reduce nonspecific binding and retain better spherical shape, the level of attractive forces acting on the immobilized polymersomes was tuned through poly­(ethylene glycol) passivation as well as decreased β-cyclodextrin content on the corresponding substrates. One significant feature of this system is the pH responsivity of the polymersomes which has been demonstrated by swelling of the immobilized vesicles at acidic condition through in situ AFM measurements. Also, light responsivity has been provided by introducing nitroveratryloxycarbonyl (NVOC) protected amine molecules as photocleavable groups to the polymersome surface before immobilization. The subsequent low-energy femtosecond pulsed laser irradiation resulted in the cleavage of NVOC groups on immobilized polymersomes which in turn led to free amino groups as an additional functionality. The freed amines were further conjugated with a fluorescent dye having an activated ester that illustrates the concept of bio/chemo recognition for a potential binding of biological compounds. In addition to the responsive nature, the mechanical stability of the analyzed polymersomes was supported by computing Young’s modulus and bending modulus of the membrane through force curves obtained by atomic force microscopy measurements. Overall, polymersomes with a robust and pH-swellable membrane combined with effective light responsive behavior are promising tools to design smart and stable compartments on surfaces for the development of microsystem devices such as chemo/biosensors

Sphere-Like Protein–Glycopolymer Nanostructures Tailored by Polyassociation

Key parameters allow a reproducible polyassociation between avidin and biotinylated glycopolymers in order to fabricate defined supramolecular nanostructures for future (bio)­medical and biotechnological applications. Thus, the polymerization efficiency of biotinylated glycopolymers in the fabrication of biohybrid structures (BHS) was investigated with regard to the influence of (i) the degree of biotinylation of the dendritic glycoarchitectures, (ii) two biotin linkers, (iii) the dendritic scaffold (perfectly branched vs hyperbranched), and (iv) the ligand–receptor stoichiometry. The adjustment of all these parameters opens the way to fabricate defined sizes of the final biohybrid structures as a multifunctional platform ready for their use in different applications. Various analytical techniques, including purification of BHS, were used to gain fundamental insights into the structural properties of the resulting protein–glycopolymer BHS. Finally, the elucidation of pivotal conformational properties of isolated BHS with defined sizes by asymmetrical flow field flow fractionation study revealed that they mainly possess spherical-/star-like properties. From this study, the fundamental knowledge can be likely transferred to other assemblies formed by molecular recognition processes (e.g., adamantane-β-cyclodextrin)

Coil-like Enzymatic Biohybrid Structures Fabricated by Rational Design: Controlling Size and Enzyme Activity over Sequential Nanoparticle Bioconjugation and Filtration Steps

Well-defined enzymatic biohybrid structures (BHS) composed of avidin, biotinylated poly­(propyleneimine) glycodendrimers, and biotinylated horseradish peroxidase were fabricated by a sequential polyassociation reaction to adopt directed enzyme prodrug therapy to protein–glycopolymer BHS for potential biomedical applications. To tailor and gain fundamental insight into pivotal properties such as size and molar mass of these BHS, the dependence on the fabrication sequence was probed and thoroughly investigated by several complementary methods (e.g., UV/vis, DLS, cryoTEM, AF4-LS). Subsequent purification by hollow fiber filtration allowed us to obtain highly pure and well-defined BHS. Overall, by rational design and control of preparation parameters, e.g., fabrication sequence, ligand–receptor stoichiometry, and degree of biotinylation, well-defined BHS with stable and even strongly enhanced enzymatic activities can be achieved. Open coil-like structures of BHS with few branches are available by the sequential bioconjugation approach between synthetic and biological macromolecules possessing similar size dimensions

Cyclodextrin-Adamantane Host–Guest Interactions on the Surface of Biocompatible Adamantyl-Modified Glycodendrimers

A series of adamantyl-modified glycodendrimers (<b>mPPI-Gx-AdaA-C</b>) was prepared in a two-step synthesis using two efficient reactions: (1) urea bond formation from amine and isocyanate and (2) reductive amination. ¹H NMR spectroscopy (host guest titration and ROESY experiments) was used to evaluate the graded effect of steric hindrance as a function of the number and type of oligosaccharide molecules and of the number of adamantyl (Ada) units on the complexation with monomeric β-cyclodextrin (β-CD). Glycosylated fourth generation PPIs showing an average substitution in adamantyl groups of 13% were found to interact with β-CD effectively, and were considered as candidates for further complexation studies with a polymeric cyclodextrin derivative (<i>poly-</i>β-CD). The host–guest interaction features of the maltosylated dense shell glycodendrimer along with the low cytotoxicity provided the rational basis for the use of these adamantyl-functionalized glycodendrimers in the design of supramolecular systems potentially useful as healthcare materials

MOESM1 of Effects of dendritic core–shell glycoarchitectures on primary mesenchymal stem cells and osteoblasts obtained from different human donors

Additional file 1. Additonal information on the investigated (oligo-)maltose-modified PEI nanoparticles