Enzyme-driven biodegradable nanomotor based on tubular-shaped polymeric vesicles

\u3cp\u3eVarious nanomotors that can mimic the motion of natural systems have recently been proposed. Yet, most designs are metal based and not applicable in biological settings. We report the first biodegradable nanomotor that moves in the presence of fuel. Tubular-shaped polymersomes with 5 wt% azide handles were assembled with catalase chemically linked to the handles. The nanotubes move autonomously in H\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e2\u3c/sub\u3e.\u3c/p\u3

Morphology under control: engineering biodegradable stomatocytes

Biodegradable nanoarchitectures, with well-defined morphological features, are of great importance for nanomedical research; however, understanding (and thereby engineering) their formation is a substantial challenge. Herein, we uncover the supramolecular potential of PEG-PDLLA copolymers by exploring the physicochemical determinants that result in the transformation of spherical polymersomes into stomatocytes. To this end, we have engineered blended polymersomes (comprising copolymers with varying lengths of PEG), which undergo solvent-dependent reorganization inducing negative spontaneous membrane curvature. Under conditions of anisotropic solvent composition across the PDLLA membrane, facilitated by the dialysis methodology, we demonstrate osmotically induced stomatocyte formation as a consequence of changes in PEG solvation, inducing negative spontaneous membrane curvature. Controlled formation of unprecedented, biodegradable stomatocytes represents the unification of supramolecular engineering with the theoretical understanding of shape transformation phenomena

Dynamic assembly of micellar mesostructures

Transient structural organization as a result of reversible interactions between individual structures is a significant characteristic of biological systems. Rearrangements of individual cells and cellular populations constantly take place as a result of interaction between different cells ‐ in response to chemical cues. Colloidal systems that operate out‐of‐equilibrium attempt to replicate the dynamic association displayed in biological systems. To probe such dynamic behavior, we present an out‐of‐equilibrium micellar nanosystem, which is able to engage in assembly and disassembly processes. Utilizing reversible disulfide chemistry via simultaneous oxidation and reduction of thiol‐functionalized micelles results in formation of dynamic meso‐structures. Such transient behavior is well‐controlled under non‐equilibrium conditions

Investigating the self-assembly and shape transformation of poly(ethylene glycol)-b-poly(d,l-lactide) (PEG-PDLLA) polymersomes by tailoring solvent-polymer interactions

The assembly of amphiphilic block copolymers in well-defined polymer nanoparticles is an intricate interplay between polymer composition, method of assembly and the properties of the organic solvent used to dissolve the polymer building blocks. Remarkably, the role of organic solvent composition has been much less studied in comparison to the other two parameters. Here we have systematically investigated the effect of organic solvent composition, namely, the ratio between tetrahydrofuran and dioxane, on the self-assembly of PEG-PDLLA copolymers into polymer vesicles and their subsequent shape change in different topologies. Uncovering such physical basis unlocks new opportunities for the development of complex nanoparticles without the need of extended polymer engineering processes

Shape characterization of polymersome morphologies via light scattering techniques

\u3cp\u3ePolymersomes, vesicles self-assembled from amphiphilic block copolymers, are well known for their robustness and for their broad applicability. Generating polymersomes of different shape is a topic of recent attention, specifically in the field of biomedical applications. To obtain information about their exact shape, tomography based on cryo-electron microscopy is usually the most preferred technique. Unfortunately, this technique is rather time consuming and expensive. Here we demonstrate an alternative analytical approach for the characterization of differently shaped polymersomes such as spheres, prolates and discs via the combination of multi-angle light scattering (MALS) and quasi-elastic light scattering (QELS). The use of these coupled techniques allowed for accurate determination of both the radius of gyration (R\u3csub\u3eg\u3c/sub\u3e) and the hydrodynamic radius (R\u3csub\u3eh\u3c/sub\u3e). This afforded us to determine the shape ratio ρ (R\u3csub\u3eg\u3c/sub\u3e/R\u3csub\u3eh\u3c/sub\u3e) with which we were able to distinguish between polymersome spheres, discs and rods.\u3c/p\u3

A filter-free blood-brain barrier model to quantitatively study transendothelial delivery of nanoparticles by fluorescence spectroscopy

\u3cp\u3eThe delivery of therapeutics to the brain is greatly hampered by the blood-brain barrier (BBB). The use of nanoparticles that can cross the BBB via the process of receptor-mediated transcytosis at blood-brain barrier endothelial cells seems a promising strategy to transport therapeutics into the brain. To screen for suitable nanocarriers, and to study the process of transcytosis, a cultured polarized monolayer of brain microvascular endothelial cells on an extracellular matrix-coated porous membrane filter is widely used as an in vitro BBB model. However, due to the adhesion of numerous types of nanoparticles to the membrane filter and within the filter pores, such a model is unsuitable for the quantification of transendothelial delivery of nanoparticles. Hence, there is a pressing need for a filter-free in vitro BBB model. Ideally, the model is inexpensive and easy to use, in order to allow for its wide use in nanomedicine and biology laboratories around the world. Here, we developed a filter-free in vitro BBB model that consists of a collagen gel covered with a monolayer of brain microvascular endothelial (hCMEC/D3) cells. The paracellular leakage of differently sized dextrans and the transcellular transport of LDL were measured to demonstrate the validity of the filter-free model. Finally, the transendothelial delivery of fluorescently-labelled PEG-P(CL-g-TMC) polymersomes that were functionalized with GM1-targeting peptides was assessed by fluorescence spectroscopy measurement of the luminal, cellular, and abluminal parts of the filter-free BBB model. Our data confirm the effectiveness of the G23 peptide to mediate transport of polymersomes across the BBB and the suitability of this filter-free in vitro model for quantification of nanoparticle transcytosis.\u3c/p\u3

Nanoreactors for green catalysis

Sustainable and environmentally benign production are key drivers for developments in the chemical industrial sector, as protecting our planet has become a significant element that should be considered for every industrial breakthrough or technological advancement. As a result, the concept of green chemistry has been recently defined to guide chemists towards minimizing any harmful outcome of chemical processes in either industry or research. Towards greener reactions, scientists have developed various approaches in order to decrease environmental risks while attaining chemical sustainability and elegancy. Utilizing catalytic nanoreactors for greener reactions, for facilitating multistep synthetic pathways in one-pot procedures, is imperative with far-reaching implications in the field. This review is focused on the applications of some of the most used nanoreactors in catalysis, namely: (polymer) vesicles, micelles, dendrimers and nanogels. The ability and efficiency of catalytic nanoreactors to carry out organic reactions in water, to perform cascade reaction and their ability to be recycled will be discussed

Formation of well-defined, functional nanotubes via osmotically induced shape transformation of biodegradable polymersomes

Polymersomes are robust, versatile nanostructures that can be tailored by varying the chemical structure of copolymeric building blocks, giving control over their size, shape, surface chemistry, and membrane permeability. In particular, the generation of nonspherical nanostructures has attracted much attention recently, as it has been demonstrated that shape affects function in a biomedical context. Until now, nonspherical polymersomes have only been constructed from nondegradable building blocks, hampering a detailed investigation of shape effects in nanomedicine for this category of nanostructures. Herein, we demonstrate the spontaneous elongation of spherical polymersomes comprising the biodegradable copolymer poly(ethylene glycol)-b-poly(d,l-lactide) into well-defined nanotubes. The size of these tubes is osmotically controlled using dialysis, which makes them very easy to prepare. To confirm their utility for biomedical applications, we have demonstrated that, alongside drug loading, functional proteins can be tethered to the surface utilizing bio-orthogonal “click” chemistry. In this way the present findings establish a novel platform for the creation of biocompatible, high-aspect ratio nanoparticles for biomedical research

Development of morphologically discrete PEG-PDLLA nanotubes for precision nanomedicine

\u3cp\u3ePrecise control over the morphological features of nanoparticles is an important requisite for their application in nanomedical research. Parameters such as size and shape have been identified as critical features for effective nanotherapeutic technologies due to their role in circulation, distribution, and internalization in vivo. Tubular PEG-PDLLA polymersomes (nanotubes) exhibit an interesting morphology with potential for immunotherapeutics, as the elongated shape can affect cell-particle interactions. Developing methodologies that permit control over the precise form of such nanotubes is important for their biomedical implementation due to the stringent physicochemical constraints for efficacious performance. Through careful control over the engineering process, we demonstrate the generation of well-defined nanotubes based on polymersomes as small as 250 and 100 nm, which can be successfully shape transformed. The quality of the resulting nanostructures was established by physical characterization using AF4-MALS and cryo-TEM. Moreover, we show the successful loading of such nanotubes with model payloads (proteins and drugs). These findings provide a promising platform for implementation in biomedical applications in which discrete structure and functionality are essential features.\u3c/p\u3

Physicochemical characterization of polymer-stabilized coacervate protocells

\u3cp\u3eThe bottom-up construction of cell mimics has produced a range of membrane-bound protocells that have been endowed with functionality and biochemical processes reminiscent of living systems. The contents of these compartments, however, experience semidilute conditions, whereas macromolecules in the cytosol exist in protein-rich, crowded environments that affect their physicochemical properties, such as diffusion and catalytic activity. Recently, complex coacervates have emerged as attractive protocellular models because their condensed interiors would be expected to mimic this crowding better. Here we explore some relevant physicochemical properties of a recently developed polymer-stabilized coacervate system, such as the diffusion of macromolecules in the condensed coacervate phase, relative to in dilute solutions, the buffering capacity of the core, the molecular organization of the polymer membrane, the permeability characteristics of this membrane towards a wide range of compounds, and the behavior of a simple enzymatic reaction. In addition, either the coacervate charge or the cargo charge is engineered to allow the selective loading of protein cargo into the coacervate protocells. Our in-depth characterization has revealed that these polymer-stabilized coacervate protocells have many desirable properties, thus making them attractive candidates for the investigation of biochemical processes in stable, controlled, tunable, and increasingly cell-like environments.\u3c/p\u3