Systematic screening of different polyglycerin‐based dienophile macromonomers for efficient nanogel formation through IEDDA inverse nanoprecipitation

Alternatives for strain‐promoted azide–alkyne cycloaddition (SPAAC) chemistries are needed because of the employment of expensive and not easily scalable precursors such as bicyclo[6.1.0]non‐4‐yne (BCN). Inverse electron demand Diels Alder (iEDDA)‐based click chemistries, using dienophiles and tetrazines, offer a more bioorthogonal and faster toolbox, especially in the biomedical field. Here, the straightforward synthesis of dendritic polyglycerin dienophiles (dPG‐dienophiles) and dPG‐methyl‐tetrazine (dPG‐metTet) as macromonomers for a fast, stable, and scalable nanogel formation by inverse nanoprecipitation is reported. Nanogel size–influencing parameters are screened such as macromonomer concentration and water‐to‐acetone ratio are screened. dPG‐norbonene and dPG‐cyclopropene show fast and stable nanogel formation in the size range of 40–200 nm and are thus used for the coprecipitation of the model protein myoglobin. High encapsulation efficiencies of more than 70% at a 5 wt% feed ratio are obtained in both cases, showing the suitability of the mild gelation chemistry for the encapsulation of small proteins

Universal polymer coatings and their representative biomedical applications

Universal polymer coatings have excellent potential for biomedical applications, because of their substrate-independent properties and versatile surface functionalization methods. The goal of this review is to summarize the state-of-art research on universal polymer coatings and their biomedical applications, as well as to present their common features including some general rules for their further development

Charged dendrimers revisited: Effective charge and surface potential of dendritic polyglycerol sulfate

We investigate key electrostatic features of charged dendrimers at hand of the biomedically important dendritic polyglycerol sulfate (dPGS) macromolecule using multi-scale computer simulations and Zetasizer experiments. In our simulation study, we first develop an effective mesoscale Hamiltonian specific to dPGS based on input from all-atom, explicit-water simulations of dPGS of low generation. Employing this in coarse-grained, implicit-solvent/explicit-salt Langevin dynamics simulations, we then study dPGS structural and electrostatic properties up to the sixth generation. By systematically mapping then the calculated electrostatic potential onto the Debye-H\"uckel form -- that serves as a basic defining equation for the effective charge -- we determine well-defined effective net charges and corresponding radii, surface charge densities, and surface potentials of dPGS. The latter are found to be up to one order of magnitude smaller than the bare values and consistent with previously derived theories on charge renormalization and weak saturation for high dendrimer generations (charges). Finally, we find that the surface potential of the dendrimers estimated from the simulations compare very well with our new electrophoretic experiments

Coordination-Induced Spin-State-Switch (CISSS) in water

We present a non-ionic water-soluble porphyrin that does not exhibit measurable aggregation even at high concentrations in water. The spin state of the corresponding nickel(II) complex changes from completely diamagnetic (low- spin) to paramagnetic (high-spin) upon addition of a strong axial ligand. This leads to a strongly reduced NMR relaxation time of the water protons even at low concentrations of the complex

Synthesis of pH-degradable polyglycerol-based nanogels by iEDDA-mediated crosslinking for encapsulation of asparaginase using inverse nanoprecipitation

Biocompatible, environmentally responsive, and scalable nanocarriers are needed for targeted and triggered delivery of therapeutic proteins. Suitable polymers, preparation methods, and crosslinking chemistries must be considered for nanogel formation. Biocompatible dendritic polyglycerol (dPG) is used in the mild, surfactant-free inverse nanoprecipitation method for nanogel preparation. The biocompatible, fast, and bioorthogonal inverse electron demand Diels-Alder (iEDDA) crosslinking chemistry is used. In this work, the synthesis of pH-degradable nanogels, based on tetrazine, norbonene, and bicyclo[6.1.0]nonyne (BCN) functionalized macromonomers, is reported. The macromonomers are non-toxic up to 2.5 mg mL−1 in three different cell lines. Nanogels are obtained in the size range of 47 to 200 nm and can be degraded within 48 h at pH 4.5 (BA-gels), and pH 3 (THP-gels), respectively. Encapsulation of asparaginase (32 kDa) yield encapsulation efficiencies of up to 93% at 5 wt.% feed. Overall, iEDDA-crosslinked pH-degradable dPG-nanogels from inverse nanoprecipitation are promising candidates for biomedical applications

Dendritic nanocarriers based on hyperbranched polymers

Hyperbranched polymers are obtained through one-step polymerization reactions and exhibit properties that are very similar to those of perfect dendrimer analogues. Therefore, hyperbranched polymers are a suitable alternative for perfect dendrimers as building blocks for dendritic nanocarrier systems. With regard to using soluble hyperbranched polymers as carrier systems, their flexible chains are a major benefit as they can adopt and compartment guest molecules. Upon encapsulation, the properties of the host decides the fate of the guest, e.g., solubility, but the host can also shield a guest from the environment and protect it, e.g., from degradation and deactivation. With regard to the advantages of using hyperbranched polymers as nanocarrier systems and their scalable synthesis, we will discuss different types of hyperbranched polymers and their application as nanocarrier systems for drugs, dyes, and other guest molecules

Algebraic Quantum Theory on Manifolds: A Haag-Kastler Setting for Quantum Geometry

Motivated by the invariance of current representations of quantum gravity under diffeomorphisms much more general than isometries, the Haag-Kastler setting is extended to manifolds without metric background structure. First, the causal structure on a differentiable manifold M of arbitrary dimension (d+1>2) can be defined in purely topological terms, via cones (C-causality). Then, the general structure of a net of C*-algebras on a manifold M and its causal properties required for an algebraic quantum field theory can be described as an extension of the Haag-Kastler axiomatic framework. An important application is given with quantum geometry on a spatial slice within the causally exterior region of a topological horizon H, resulting in a net of Weyl algebras for states with an infinite number of intersection points of edges and transversal (d-1)-faces within any neighbourhood of the spatial boundary S^2.Comment: 15 pages, Latex; v2: several corrections, in particular in def. 1 and in sec.

Micro- and nanogels with labile crosslinks – from synthesis to biomedical applications

Micro- or nanosized three-dimensional crosslinked polymeric networks have been designed and described for various biomedical applications, including living cell encapsulation, tissue engineering, and stimuli responsive controlled delivery of bioactive molecules. For most of these applications, it is necessary to disintegrate the artificial scaffold into nontoxic residues with smaller dimensions to ensure renal clearance for better biocompatibility of the functional materials. This can be achieved by introducing stimuli- cleavable linkages into the scaffold structures. pH, enzyme, and redox potential are the most frequently used biological stimuli. Moreover, some external stimuli, for example light and additives, are also used to trigger the disintegration of the carriers or their assembly. In this review, we highlight the recent progress in various chemical and physical methods for synthesizing and crosslinking micro- and nanogels, as well as their development for incorporation of cleavable linkages into the network of micro- and nanogels

Polyester-Based, Biodegradable Core-Multishell Nanocarriers for the Transport of Hydrophobic Drugs

A water-soluble, core-multishell (CMS) nanocarrier based on a new hyperbranched polyester core building block was synthesized and characterized towards drug transport and degradation of the nanocarrier. The hydrophobic drug dexamethasone was encapsulated and the enzyme-mediated biodegradability was investigated by NMR spectroscopy. The new CMS nanocarrier can transport one molecule of dexamethasone and degrades within five days at a skin temperature of 32 °C to biocompatible fragments

Biocatalytic Synthesis Using Self-Assembled Polymeric Nano- and Microreactors

Biocatalysis is increasingly being explored for the sustainable development of green industry. Though enzymes show great industrial potential with their high efficiency, specificity, and selectivity, they suffer from poor usability and stability under abiological conditions. To solve these problems, researchers have fabricated nano- and micro-sized biocatalytic reactors based on the self-assembly of various polymers, leading to highly stable, functional, and reusable biocatalytic systems. This Review highlights recent progress in self-assembled polymeric nano- and microreactors for biocatalytic synthesis, including polymersomes, reverse micelles, polymer emulsions, Pickering emulsions, and static emulsions. We categorize these reactors into monophasic and biphasic systems and discuss their structural characteristics and latest successes with representative examples. We also consider the challenges and potential solutions associated with the future development of this field