Correction to “Hollow Capsules with Multiresponsive Valves for Controlled Enzymatic Reactions”

Correction to “Hollow Capsules with Multiresponsive Valves for Controlled Enzymatic Reactions

Immunomodulatory Effects of Dendritic Poly(ethyleneimine) Glycoarchitectures on Human Multiple Myeloma Cell Lines, Mesenchymal Stromal Cells, and in Vitro Differentiated Macrophages for an Ideal Drug Delivery System in the Local Treatment of Multiple Myeloma

The use of a drug delivery system (DDS) represents a novel therapeutic approach in the treatment of multiple myeloma in bone lesion. We show the immunomodulatory effects of anionic and cationic dendritic poly­(ethyleneimine) glycoarchitectures (PEI-DGAs) on human myeloma cell lines and cells in their microenvironment, in vitro differentiated macrophages, and mesenchymal stromal cells (MSCs). PEI-DGAs do not influence the secretion of IL-6, which is a major growth and survival factor in multiple myeloma. Cationic PEI-DGAs in turn have cytostatic properties on multiple myeloma cell lines. Anionic PEI-DGAs induce the secretion of proinflammatory cytokines IL-1β, TNFα, and IL-6 in macrophages and MSCs, whereas cationic PEI-DGAs do not. Macrophages and MSCs show remarkably high cell viability in the presence of high concentration of PEI-DGAs. RNA sequencing of MSCs exposed to cationic PEI-DGAs supports the hypothesis that smaller cationic PEI-DGAs are less toxic and could improve osteogenic differentiation in an ideal DDS

Synthesis of Well-Defined Photo-Cross-Linked Polymeric Nanocapsules by Surface-Initiated RAFT Polymerization

Narrowly distributed hollow polymeric nanocapsules (PtBMA-co-PDMIPM-b-PHPMA), with the size of 450 or 900 nm, were first synthesized by surface-initiated reversible addition–fragmentation chain transfer (RAFT) polymerization exploiting silica nanoparticles as sacrificial templates and 2,3-dimethylmaleic imidopropyl methacrylate (DMIPM) as a photo-cross-linker. First, silica nanoparticles were amino functionalized by aminosilane agents, and then the dithiocarbonate chain transfer agent (CTA) was anchored via activated R-groups to the amino-functionalized surface of silica nanoparticles. This surface layer of CTA groups was then used to grow linear copolymers and block copolymers by RAFT polymerization leading to a core–shell morphology. TEM and GPC results indicated that the thickness of the shell can be well governed by simply controlling the molecular weight of the grafted copolymer. Finally, after photo-cross-linking and etching the silica core with NH4F/HF buffer, hollow nanocapsules were obtained, of which the morphology and composition were confirmed by employing a range of techniques, such as TEM, cryo-TEM, DLS, SEM, XPS, TGA, FTIR, GPC, and UV–vis spectroscopy. Thus, robust and narrowly distributed polymeric nanocapsules with size of 450 nm and a wall thickness 10 nm based on the grafted block copolymer PtBMA-co-PDMIPM-b-PHPMA having Mn = 19 500 g/mol (GPC) could be prepared

Molecular Dynamics in Poly(ethene-<i>a</i><i>lt</i>-<i>N</i>-alkylmaleimide)s As Studied by Broadband Dielectric Spectroscopy

Broadband dielectric spectroscopy has been used to analyze the molecular dynamics in a set of nine poly(ethene-alt-N-alkylmaleimide)s. The polymers were studied in the frequency range from 0.1 Hz to 10 MHz and at temperatures between 120 and 500 K. The alternating maleimide copolymers possess alkyl side chains varying in length from methyl to octadecyl. Four relaxation processes are observed:  (i) a (secondary) β-relaxation corresponding to librational fluctuations of the terminal end group of the alkyl side chain, (ii) the α‘-relaxation being assigned to a relaxation of the side chain, (iii) the dynamic glass transition (α-relaxation), being designated to motions of the succinimide ring, and (iv) the αs-relaxation reflecting cooperative fluctuations of an ensemble of about 2−3 maleimide rings in an underlying helical superstructure. This model is supported by calorimetric measurements and published nuclear magnetic resonance data

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

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

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

Kinetics of Nonideal Hyperbranched Polymerizations. 2. Kinetic Analysis of the Polycondensation of 3,5-Bis(trimethylsiloxy)benzoyl chloride Using NMR Spectroscopy^†

The kinetics of the polycondensation of 3,5-bis(trimethylsiloxy)benzoyl chloride (BTMSBCl) was investigated. 1D and 2D NMR techniques were applied to achieve a complete signal assignment of the structural units of the resulting polymer (poly(3,5-dihydroxybenzoic acid), PDHBA), which was obtained after hydrolysis of the trimethylsiloxy and the acid chloride groups. Furthermore, the diads could be identified. After quantification of the signals by 13C NMR spectroscopy, a data set of ratios of structural units as a function of the conversion had been studied with respect of the kinetics of the system and their resulting structural composition. Since the data do not follow the ideal conversion dependence, the relative rate constants of the 12 different basic reaction steps were determined by simulation, which fit the obtained data best. A study of the sensitivity of the reaction curves to changes in the individual rate constants showed large differences and helped to distinguish the importance of the different basic reactions to the overall reaction. One kinetic situation was identified as dominant. The deviations (from the ideal conversion dependence) were explained by different electronic effects on the reaction sites caused by the successive substitution of siloxy and benzoyl chloride groups by ester groups on the aromatic ring. Analysis of the data for the diads indicated no further kinetic effect

From 1D Rods to 3D Networks: A Biohybrid Topological Diversity Investigated by Asymmetrical Flow Field-Flow Fractionation

Biohybrid structures formed by noncovalent interaction between avidin as a bridging unit and biotinylated glycodendrimers based on poly­(propyleneimine) (GD-B) have potential for biomedical application. Therefore, an exact knowledge about molar mass, dispersity, size, shape, and molecular structure is required. Asymmetrical flow field-flow fractionation (AF4) was applied to separate pure and assembled macromolecules according to their diffusion coefficients. The complex biohybrid structures consist of single components (avidin, differently valent GD-B) and nanostructures. These nanostructures were systematically studied depending on the degree of biotinylation and ligand–receptor stoichiometry by AF4 in combination with dynamic and static light scattering detection. This enables the quantification of composition and calculation of molar masses and radii, which were used to analyze scaling properties and apparent density of the formed structures. These data are compared to hydrodynamic radii obtained by applying the retention theory to the AF4 data. It is shown that depending on their architecture the molecular shape of biohybrid structures is changed from rod-like to spherical toward network-like behavior