Lea Messager

Novel aspects of encapsulation and delivery using polymersomes

Polymersomes are nanoscopic (e.g. nanometer-sized) vesicles formed by amphiphilic block copolymers. They represent the more robust and versatile macromolecular counterparts to the well-established lipid vesicles or liposomes. Recently, considerable efforts have been made to produce them in a uniform and functional manner. New techniques such as artificial endocytosis and electroporation have also been developed to achieve payload encapsulation. In this mini-review, we discuss these and other recent developments in making polymersomes an actual alternative for biomedical applications.

Biomimetic Hybrid Nanocontainers with Selective Permeability

Abstract Chemistry plays a crucial role in creating synthetic analogues of biomacromolecular structures. Of particular scientific and technological interest are biomimetic vesicles that are inspired by natural membrane compartments and organelles but avoid their drawbacks, such as membrane instability and limited control over cargo transport across the boundaries. In this study, completely synthetic vesicles were developed from stable polymeric walls and easy‐to‐engineer membrane DNA nanopores. The hybrid nanocontainers feature selective permeability and permit the transport of organic molecules of 1.5 nm size. Larger enzymes (ca. 5 nm) can be encapsulated and retained within the vesicles yet remain catalytically active. The hybrid structures constitute a new type of enzymatic nanoreactor. The high tunability of the polymeric vesicles and DNA pores will be key in tailoring the nanocontainers for applications in drug delivery, bioimaging, biocatalysis, and cell mimicry.

Nanoscale detection of metal-labeled copolymers in patchy polymersomes

We report the synthesis of polymersome-forming block copolymers using two different synthetic routes based on Atom Transfer Radical Polymerization (ATRP) and Reversible Addition Fragmentation chain Transfer (RAFT) polymerization, respectively. Functionalization with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) allowed the block copolymer chains to be labelled with electron-dense metal ions (e.g. indium). The resulting metal-conjugated copolymers can be visualized by transmission electron microscopy with single chain resolution, hence enabling the study of polymer/polymer immiscibility and phase separation on the nano-scale.

Molecular engineering of polymersome surface topology

Self-assembling vesicles made of copolymer mimics biological systems. Biological systems exploit self-assembly to create complex structures whose arrangements are finely controlled from the molecular to mesoscopic level. We report an example of using fully synthetic systems that mimic two levels of self-assembly. We show the formation of vesicles using amphiphilic copolymers whose chemical nature is chosen to control both membrane formation and membrane-confined interactions. We report polymersomes with patterns that emerge by engineering interfacial tension within the polymersome surface. This allows the formation of domains whose topology is tailored by chemical synthesis, paving the avenue to complex supramolecular designs functionally similar to those found in viruses and trafficking vesicles.Biological systems exploit self-assembly to create complex structures whose arrangements are finely controlled from molecular to mesoscopic level. Herein we report an example of using fully synthetic systems that mimic two levels of self-assembly. We show the formation of vesicles using amphiphilic copolymers whose chemical nature is chosen to control both membrane formation and membrane-confined interactions. We report polymersomes with patterns that emerge by engineering interfacial tension within the polymersome surface. This allows the formation of domains whose topology is tailored by the chemical synthesis paving the avenue to complex supramolecular designs functionally similar to those found in viruses and trafficking vesicles. Living systems are the result of a very precise and balanced hierarchical organisation of molecules and macromolecules. These are constructed with specific chemical signatures that direct supramolecular interaction between themselves and/or with water. Such interactions, typically low in energy (i.e. tens of kTs), allow the formation of mesoscale architectures with exquisite spatial and temporal control. This process known as self-assembly is very much ubiquitous in Nature and is at the core of any biological transformation [1]. Alongside such a positional control of molecules, Nature creates specific energy pools by enclosing chemicals into aqueous volumes using gated compartments [2]. Both compartmentalisation and positional self-assembly create structures whose surfaces express several chemistries performing their function holistically according to specific topological interactions. Biological surfaces are far from homogenous systems and organise their components according to specific (quasi)regular patterns. It is now well-established that any cell membrane has a mosaic-like structure made of dynamic nanoscale assemblies of lipids, sterols, glycols, and proteins collectively known as rafts and that these rafts control membrane signalling and trafficking [3]. Such a topological control is also conserved in smaller biological structures such as viruses, synaptic vesicles, lipoproteins and bacteria. In these, key ligands are combined into topologies with super-symmetric arrangements such as in most nonenveloped viruses[4], or have semi-ordered topologies such as in lipoproteins[5] or even into Turing-like patterns such as in most enveloped viruses [6] and endogenous trafficking vesicles [7]. Surface topology is not stochastic and is the result of an evolutionary drive often associated with a specific function. Viruses, for example, change their surface topology during maturation from a noninfectious, almost inert assembly, to an infectious cell-active structure capable of entering cells

Glyconanoparticles with controlled morphologies and their interactions with a dendritic cell lectin

Well-defined amphiphilic block glycopolymers with equal mannose content have been self-assembled in aqueous solution to form glyconanoparticles with different morphologies. The size and shape of nanoparticles have significant effects on the interactions with the dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN; CD209), characterized using a surface plasmon resonance spectrometer (SPR).

Vesicles in Multiple Shapes: Fine-Tuning Polymersomes’ Shape and Stability by Setting Membrane Hydrophobicity

Amphiphilic block-copolymers are known to self-assemble into micelles and vesicles. In this paper, we discuss the multiple options between and beyond these boundaries using amphiphilic AB diblock and ABC triblock copolymers. We adjust the final structure reached by the composition of the mixture, by the preparation temperature, and by varying the time-scale of formation. This leads to the formation of vesicles and micelles, but also internal micelles in larger sheets, lamellar vesicles, and closed tubes, thus broadening the amount of self-assembly structures available and deepening our understanding of them.

Corrigendum: Self-Assembly of Amphiphilic Block Copolypeptoids - Micelles, Worms and Polymersomes.

Scientific Reports 6: Article number: 33491; published online: 26 September 2016; updated: 19 December 2016