Tuning the upper critical solution temperature behavior of poly(methyl methacrylate) in aqueous ethanol by modification of an activated ester comonomer

A statistical copolymer of methyl methacrylate (MMA) and pentafluorophenyl methacrylate (PFPMA, 6 mol%) exhibits upper critical solution temperature (UCST) behavior in aqueous ethanol solutions tunable by post-polymerization modification with different amines. The phase transition behavior of the obtained copolymers in aqueous ethanol was evaluated in detail. As expected, all copolymers reveal an upper critical solution temperature with 55 vol% or higher ethanol content. Furthermore, the solubility in aqueous ethanol of the copolymer can be increased by the introduction of hydrophilic moieties. When hydrophobic substituents are introduced a decrease in solubility was observed with low content of ethanol and an increase in solubility when adding more ethanol. As such, the thermoresponsive behavior of PMMA can be significantly altered by post-modification of 6 mol% of the reactive comonomer units. The hysteresis of the polymer phase transitions between heating and cooling was found to be strongly dependent on the polarity of the amine substituent and the ethanol/water ratio. The metastability of the hysteresis is addressed based on isothermal turbidity studies

Enhanced Diffusion of Glucose-Fueled Janus Particles

The search for biocompatible fuels to induce autonomous motion in particles is a long-standing challenge in the field of nanorobotics. Hydrogen peroxide (H₂O₂) is the most utilized fuel for micro/nanomotors, although its cytotoxicity impedes its application in a biomedical context. Biocompatibility not only involves the adjustment of the motor, which should convert the energy from a stable compound into locomotion, but also requires new fabrication methods and the generation of nontoxic products resulting from fuel consumption. To address this challenge, we present the assembly and enhanced diffusion of sub-micron-sized Janus particles that feature one hemisphere decorated with the enzyme pair glucose oxidase and catalase and the use of glucose as fuel. It is found that the colloids exhibit glucose-concentration-dependent enhanced diffusion behavior, thus bringing the concept of nanomachines closer to use in biomedical applications

Planar and Cell Aggregate-Like Assemblies Consisting of Microreactors and HepG2 Cells

The assembly of microreactors has made considerable progress toward the fabrication of artificial cells. However, their characterization remains largely limited to buffer solution-based assays in the absence of their natural role modelthe biological cells. Herein, the combination of microreactors with HepG2 cells either in planar cell cultures or in the form of cell aggregates is reported. Alginate (Alg)-based microreactors loaded with catalase are assembled by droplet microfluidics, and their activity is confirmed. The acceptance of polymer-coated ∼40 μm Alg particles by proliferating HepG2 cells is depending on the terminating polymer layer. When these functional microreactors are cocultured with HepG2 cells, they can be employed for detoxification, that is, hydrogen peroxide removal, and by doing so, they assist the cells to survive. This report is among the first successful combination of microreactors with biological cells, that is, HepG2 cells, contributing to the fundamental understanding of integrating synthetic and biological partners toward the maturation of this semisynthetic concept for biomedical applications

Phospholipid-Block Copolymer Hybrid Vesicles with Lysosomal Escape Ability

The success of nanoparticulate formulations in drug delivery depends on various aspects including their toxicity, internalization, and intracellular location. Vesicular assemblies consisting of phospholipids and amphiphilic block copolymers are an emerging platform, which combines the benefits from liposomes and polymersomes while overcoming their challenges. We report the synthesis of poly(cholesteryl methacrylate)- block-poly(2-(dimethylamino) ethyl methacrylate) (pCMA- b-pDMAEMA) block copolymers and their assembly with phospholipids into hybrid vesicles. Their geometry, their ζ-potential, and their ability to adsorb onto polymer-coated surfaces were assessed. Giant unilamellar vesicles were employed to confirm the presence of both the phospholipids and the block copolymer in the same membrane. Furthermore, the cytotoxicity of selected hybrid vesicles was determined in RAW 264.7 mouse macrophages, primary rat Kupffer cells, and human macrophages. The internalization and lysosomal escape ability of the hybrid vesicles were confirmed using RAW 264.7 mouse macrophages. Taken together, our findings illustrate that the reported hybrid vesicles are a promising complementary drug delivery platform for existing liposomes and polymersomes

Platinum Nanoparticle-Based Microreactors as Support for Neuroblastoma Cells

Excitotoxicity is a common phenomenon in several neurological diseases, associated with an impaired clearance of synaptically released glutamate, which leads to an overactivation of postsynaptic glutamate receptors. This will, in turn, start an intracellular cascade of neurotoxic events, which include exacerbated production of reactive oxygen species and ammonia toxicity. We report the assembly of microreactors equipped with platinum nanoparticles as artificial enzymes and polymer terminating layers including poly­(dopamine). The biological response to these microreactors is assessed in human neuroblastoma cell culture. The microreactors’ function to deplete hydrogen peroxide (H₂O₂) and ammonia is confirmed. While the proliferation of the cells depends on the number of microreactors present, no inherent toxicity is found. Furthermore, the microreactors are able to ameliorate the effects of excitotoxicity in cell culture by scavenging H₂O₂ and ammonia, thus having the potential to provide a therapeutic approach for several neurological diseases in which excitotoxicity is observed

Phospholipid–Block Copolymer Hybrid Vesicles with Lysosomal Escape Ability

The success of nanoparticulate formulations in drug delivery depends on various aspects including their toxicity, internalization, and intracellular location. Vesicular assemblies consisting of phospholipids and amphiphilic block copolymers are an emerging platform, which combines the benefits from liposomes and polymersomes while overcoming their challenges. We report the synthesis of poly­(cholesteryl methacrylate)-<i>block</i>-poly­(2-(dimethylamino) ethyl methacrylate) (pCMA-<i>b</i>-pDMAEMA) block copolymers and their assembly with phospholipids into hybrid vesicles. Their geometry, their ζ-potential, and their ability to adsorb onto polymer-coated surfaces were assessed. Giant unilamellar vesicles were employed to confirm the presence of both the phospholipids and the block copolymer in the same membrane. Furthermore, the cytotoxicity of selected hybrid vesicles was determined in RAW 264.7 mouse macrophages, primary rat Kupffer cells, and human macrophages. The internalization and lysosomal escape ability of the hybrid vesicles were confirmed using RAW 264.7 mouse macrophages. Taken together, our findings illustrate that the reported hybrid vesicles are a promising complementary drug delivery platform for existing liposomes and polymersomes