Controlling Polymer Morphologies by Intramolecular and Intermolecular Dynamic Covalent Iron(III)/Catechol Complexation-From Polypeptide Single Chain Nanoparticles to Hydrogels.

Responsive biomaterials, tunable from the molecular to the macroscopic scale, are attractive for various applications in nanotechnology. Herein, a long polypeptide chain derived from the abundant serum protein human serum albumin is cross-linked by dynamic-coordinative iron(III)/catechol bonds. By tuning the binding stoichiometry and the pH, reversible intramolecular folding into polypeptide nanoparticles with controllable sizes is achieved. Moreover, upon varying the stoichiometry, intermolecular cross-links become predominant yielding smart and tunable macroscopic protein hydrogels. By adjusting the intra- and intermolecular interactions, biocompatible and biodegradable materials are formed with varying morphologies and dimensions covering several lengths scales featuring rapid gelation without toxic reagents, fast and autonomous self-healing, tunable mechanical properties, and high adaptability to local environmental conditions. Such material characteristics can be particularly attractive for tissue engineering approaches to recreate soft tissues matrices with highly customizable features in a fast and simple fashion.

Reversing Aß Fibrillation and Inhibiting Aß Primary Neuronal Cell Toxicity Using Amphiphilic Polyphenylene Dendrons.

Uncontrolled amyloid-beta (Aß) fibrillation leads to the deposition of neurotoxic amyloid plaques and is associated with Alzheimer's disease. Inhibiting Aß monomer fibrillation and dissociation of the formed fibers is regarded as a promising therapeutic strategy. Here, amphiphilic polyphenylene dendrons (APDs) are demonstrated to interrupt Aß assembly and reduce Aß-cell interactions. Containing alternating negatively charged sulfonic acid and hydrophobic n-propyl peripheral groups, APDs bind to the secondary structure of the Aß aggregates, inhibiting fibrillation and disassemble the already formed Aß fibrils. APDs reveal vesicular cellular uptake in endosomes as well as cell compatibility for endothelial and neuronal cells, and significantly reduce Aß-induced neuron cytotoxicity in vitro. Moreover, they are transported into the brain and successfully cross the blood-brain barrier after systemic application in mice, indicating their high potential to inhibit Aß fibrillation in vivo, which can be beneficial for developing therapeutic strategy for Alzheimer's disease.

DNA-Polymer Nanostructures by RAFT Polymerization and Polymerization-Induced Self-Assembly.

Nanostructures derived from amphiphilic DNA-polymer conjugates have emerged prominently due to their rich self-assembly behavior; however, their synthesis is traditionally challenging. Here, we report a novel platform technology towards DNA-polymer nanostructures of various shapes by leveraging polymerization-induced self-assembly (PISA) for polymerization from single-stranded DNA (ssDNA). A "grafting from" protocol for thermal RAFT polymerization from ssDNA under ambient conditions was developed and utilized for the synthesis of functional DNA-polymer conjugates and DNA-diblock conjugates derived from acrylates and acrylamides. Using this method, PISA was applied to manufacture isotropic and anisotropic DNA-polymer nanostructures by varying the chain length of the polymer block. The resulting nanostructures were further functionalized by hybridization with a dye-labelled complementary ssDNA, thus establishing PISA as a powerful route towards intrinsically functional DNA-polymer nanostructures.

Sequence Programming with Dynamic Boronic Acid/Catechol Binary Codes.

The development of a synthetic code that enables a sequence programmable feature like DNA represents a key aspect toward intelligent molecular systems. We developed herein the well-known dynamic covalent interaction between boronic acids (BAs) and catechols (CAs) into synthetic nucleobase analogs. Along a defined peptide backbone, BA or CA residues are arranged to enable sequence recognition to their complementary strand. Dynamic strand displacement and errors were elucidated thermodynamically to show that sequences are able to specifically select their partners. Unlike DNA, the pH dependency of BA/CA binding enables the dehybridization of complementary strands at pH 5.0. In addition, we demonstrate the sequence recognition at the macromolecular level by conjugating the cytochrome c protein to a complementary polyethylene glycol chain in a site-directed fashion.

Zirconyl Clindamycinphosphate Antibiotic Nanocarriers for Targeting Intracellular Persisting Staphylococcus aureus.

[ZrO]2+[CLP]2- (CLP: clindamycinphosphate) inorganic-organic hybrid nanoparticles (IOH-NPs) represent a novel strategy to treat persisting, recurrent infections with multiresistant Staphylococcus aureus. [ZrO]2+[CLP]2- is prepared in water and contains the approved antibiotic with unprecedented high load (82 wt % CLP per nanoparticle). The IOH-NPs result in 70-150-times higher antibiotic concentrations at difficult-to-reach infection sites, offering new options for improved drug delivery for chronic and difficult-to-treat infections.