Biocatalytically Active Thin Films via Self-Assembly of 2-Deoxy-d-ribose-5-phosphate Aldolase-Poly(N-isopropylacrylamide) Conjugates.

2-Deoxy-d-ribose-5-phosphate aldolase (DERA) is a biocatalyst that is capable of converting acetaldehyde and a second aldehyde as acceptor into enantiomerically pure mono- and diyhydroxyaldehydes, which are important structural motifs in a number of pharmaceutically active compounds. However, substrate as well as product inhibition requires a more-sophisticated process design for the synthesis of these motifs. One way to do so is to the couple aldehyde conversion with transport processes, which, in turn, would require an immobilization of the enzyme within a thin film that can be deposited on a membrane support.

Immobilization of 2-Deoxy-d-ribose-5-phosphate Aldolase in Polymeric Thin Films via the Langmuir-Schaefer Technique.

A synthetic protocol for the fabrication of ultrathin polymeric films containing the enzyme 2-deoxy-d-ribose-5-phosphate aldolase from Escherichia coli (DERA) is presented. Ultrathin enzymatically active films are useful for applications in which only small quantities of active material are needed and at the same time quick response and contact times without diffusion limitation are wanted. We show how DERA as an exemplary enzyme can be immobilized in a thin polymer layer at the air-water interface and transferred to a suitable support by the Langmuir-Schaefer technique under full conservation of enzymatic activity.

Transiently thermoresponsive polymers and their applications in biomedicine.

The focus of this review is on the class of transiently thermoresponsive polymers. These polymers are thermoresponsive, but gradually lose this property upon chemical transformation - often a hydrolysis reaction - in the polymer side chain or backbone. An overview of the different approaches used for the design of these polymers along with their physicochemical properties is given.

Core/shell protein-reactive nanogels via a combination of RAFT polymerization and vinyl sulfone postmodification.

Aim: A promising nanogel vaccine platform was expanded toward antigen conjugation.

Materials & Methods: Block copolymers containing a reactive ester solvophobic block and a PEG-like solvophilic block were synthesized via reversible addition-fragmentation chain-transfer polymerization. Following self-assembly in DMSO, the esters allow for core-crosslinking and hydrophilization by amide bond formation with primary amines.

Well-Defined Polymer-Paclitaxel Prodrugs by a Grafting-from-Drug Approach.

We report on the design of a polymeric prodrug of the anticancer agent paclitaxel (PTX) by a grafting-from-drug approach. A chain transfer agent for reversible addition fragmentation chain transfer (RAFT) polymerization was efficiently and regioselectively linked to the C2' position of paclitaxel, which is crucial for its bioactivity. Subsequent RAFT polymerization of a hydrophilic monomer yielded well-defined paclitaxel-polymer conjugates with high drug loading, water solubility, and stability.

pH-degradable imidazoquinoline-ligated nanogels for lymph node-focused immune activation.

Agonists of Toll-like receptors (TLRs) are potent activators of the innate immune system and hold promise as vaccine adjuvant and for anticancer immunotherapy. Unfortunately, in soluble form they readily enter systemic circulation and cause systemic inflammatory toxicity. Here we demonstrate that by covalent ligation of a small-molecule imidazoquinoline-based TLR7/8 agonist to 50-nm-sized degradable polymeric nanogels the potency of the agonist to activate TLR7/8 in in vitro cultured dendritic cells is largely retained.

pH-Degradable Mannosylated Nanogels for Dendritic Cell Targeting.

We report on the design of glycosylated nanogels via core-cross-linking of amphiphilic non-water-soluble block copolymers composed of an acetylated glycosylated block and a pentafluorophenyl (PFP) activated ester block prepared by reversible addition-fragmentation (RAFT) polymerization. Self-assembly, pH-sensitive core-cross-linking, and removal of remaining PFP esters and protecting groups are achieved in one pot and yield fully hydrated sub-100 nm nanogels. Using cell subsets that exhibit high and low expression of the mannose receptor (MR) under conditions that suppress active endocytosis, we show that mannosylated but not galactosylated nanogels can efficiently target the MR that is expressed on the cell surface of primary dendritic cells (DCs).

Super Resolution Imaging of Nanoparticles Cellular Uptake and Trafficking.

Understanding the interaction between synthetic nanostructures and living cells is of crucial importance for the development of nanotechnology-based intracellular delivery systems. Fluorescence microscopy is one of the most widespread tools owing to its ability to image multiple colors in native conditions. However, due to the limited resolution, it is unsuitable to address individual diffraction-limited objects.

A Generic Polymer-Protein Ligation Strategy for Vaccine Delivery.

Although the field of cancer immunotherapy is intensively investigated, there is still a need for generic strategies that allow easy, mild and efficient formulation of vaccine antigens. Here we report on a generic polymer-protein ligation strategy to formulate protein antigens into reversible polymeric conjugates for enhanced uptake by dendritic cells and presentation to CD8 T-cells. A N-hydroxypropylmethacrylamide (HPMA)-based copolymer was synthesized via RAFT polymerization followed by introduction of pyridyldisulfide moieties.

Spontaneous Protein Adsorption on Graphene Oxide Nanosheets Allowing Efficient Intracellular Vaccine Protein Delivery.

Nanomaterials hold potential of altering the interaction between therapeutic molecules and target cells or tissues. High aspect ratio nanomaterials in particular have been reported to possess unprecedented properties and are intensively investigated for their interaction with biological systems. Graphene oxide (GOx) is a water-soluble graphene derivative that combines high aspect ratio dimension with functional groups that can be exploited for bioconjugation.

Engineering Polymer Hydrogel Nanoparticles for Lymph Node-Targeted Delivery.

The induction of antigen-specific adaptive immunity exclusively occurs in lymphoid organs. As a consequence, the efficacy by which vaccines reach these tissues strongly affects the efficacy of the vaccine. Here, we report the design of polymer hydrogel nanoparticles that efficiently target multiple immune cell subsets in the draining lymph nodes.

Acid-Labile Thermoresponsive Copolymers That Combine Fast pH-Triggered Hydrolysis and High Stability under Neutral Conditions.

Biodegradable polymeric materials are intensively used in biomedical applications. Of particular interest for drug-delivery applications are polymers that are stable at pH 7.4, that is, in the blood stream, but rapidly hydrolyze under acidic conditions, such as those encountered in the endo/lysosome or the tumor microenvironment.

Degradable ketal-based block copolymer nanoparticles for anticancer drug delivery: a systematic evaluation.

Low solubility of potent (anticancer) drugs is a major driving force for the development of noncytotoxic, stimuli-responsive nanocarriers, including systems based on amphiphilic block copolymers. In this regard, we investigated the potential of block copolymers based on 2-hydroxyethyl acrylate (HEA) and the acid-sensitive ketal-containing monomer (2,2-dimethyl-1,3-dioxolane-4-yl)methyl acrylate (DMDMA) to form responsive drug nanocarriers. Block copolymers were successfully synthesized by sequential reversible addition-fragmentation chain transfer (RAFT) polymerization, in which we combined a hydrophilic poly(HEA)x block with a (responsive) hydrophobic poly(HEAm-co-DMDMAn)y copolymer block.