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.

Poly(dopamine) (PDA) coatings have recently attracted considerable interest for a variety of applications. Here, we investigate the film deposition of dopamine mixed with a nonionic polymer (i.e., poly(ethylene glycol) (PEG), poly(vinyl alcohol) (PVA), and poly(N-vinyl pyrrolidone) (PVP)) onto silica substrates using X-ray photoelectron spectroscopy and quartz crystal microbalance. Furthermore, we assess the possibility of coating silica colloids to yield polymer capsules and liposomes with these mixtures. We found that mixed PDA/PEG and PDA/PVA films are deposited without the need for a covalent linker such as an amine or thiol. We also discovered the first material, namely, PVP, that can suppress PDA film assembly. These fundamental findings give further insight into PDA film properties and contribute to establish PDA as a widely applicable coating.

Cell mimicry is an approach which aims at substituting missing or lost activity. In this context, the goal of artificial organelles is to provide intracellularly active nanoreactors to affect the cellular performance. So far, only a handful of reports discuss concepts addressing this challenge based on single-component reactors. Here, the assembly of nanoreactors equipped with glucose oxidase (GOx)-loaded liposomal subunits coated with a poly(dopamine) polymer layer and RGD targeting units is reported. When comparing different surface modifications, the uptake of the nanoreactors by endothelial cells and macrophages with applied shear stress is confirmed without inherent cytotoxicity. Furthermore, the encapsulation and preserved activity of GOx within the nanoreactors is shown. The intracellular activity is demonstrated by exposing macrophages with internalized nanoreactors to glucose and assessment of the cell viability after 6 and 24 h. The macrophage viability is found to be reduced due to the intracellularly produced hydrogen peroxide by GOx. This report on the first intracellular active subcompartmentalized nanoreactors is a considerable step in therapeutic cell mimicry.

Biocatalytic intracellular active nanoreactors (artificial organelles) aim to support their host cells. Here, we report the first successful micelle-based artificial organelles containing a salen−manganese complex (EUK) as catalase mimic with intracellular activity in HepG2 cells to act as reactive oxygen species (ROS) scavengers. Four different EUKs were synthesized and compared in their ability to convert hydrogen peroxide to water and oxygen as free compounds and when encapsulated into micelles assembled from the amphiphilic block copolymer poly(cholesteryl methacrylate)-block-poly(2-(dimethylamino)ethyl methacrylate). An EUK candidate with an asymmetric substitution of chemical groups at the ortho and the meta position (EUK-B) was identified as lead candidate. HepG2 cells continued proliferating when preincubated with low concentrations of EUK-B-containing micelles (M B ). Importantly, HepG2 cells equipped with M B showed improved viability compared to the controls when stressed with paraquat, a compound that induces ROS generation. The intracellular activity of M B was supported by lower amounts of intracellular detectable ROS. This first report on the combination of artificial enzymes and artificial organelles further extends the opportunities in therapeutic cell mimicry.

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.