Christophe A. Monnier

Insertion of Nanoparticle Clusters into Vesicle Bilayers

A major contemporary concern in developing effective liposome-nanoparticle hybrids is the present inclusion size limitation of nanoparticles between vesicle bilayers, which is considered to be around 6.5 nm in diameter. In this article, we present experimental observations backed by theoretical considerations which show that greater structures can be incorporated within vesicle membranes by promoting the clustering of nanoparticles before liposome formation. Cryo-transmission electron microscopy and cryo-electron tomography confirm these observations at unprecedented detail and underpin that the liposome membranes can accommodate flexible structures of up to 60 nm in size. These results imply that this material is more versatile in terms of inclusion capabilities and consequently widens the opportunities in developing multivalent vesicles for nanobiotechnology applications.

Filling polymersomes with polymers by peroxidase-catalyzed atom transfer radical polymerization.

Polymersomes that encapsulate a hydrophilic polymer are prepared by conducting biocatalytic atom transfer radical polymerization (ATRP) in these hollow nanostructures. To this end, ATRPase horseradish peroxidase (HRP) is encapsulated into vesicles self-assembled from poly(dimethylsiloxane)-block-poly(2-methyl-2-oxazoline) (PDMS-b-PMOXA) diblock copolymers. The vesicles are turned into nanoreactors by UV-induced permeabilization with a hydroxyalkyl phenone and used to polymerize poly(ethylene glycol) methyl ether acrylate (PEGA) by enzyme-catalyzed ATRP. As the membrane of the polymersomes is only permeable for the reagents of ATRP but not for macromolecules, the polymerization occurs inside of the vesicles and fills the polymersomes with poly(PEGA), as evidenced by (1) H NMR. Dynamic and static light scattering show that the vesicles transform from hollow spheres to filled spheres during polymerization. Transmission electron microscopy (TEM) and cryo-TEM imaging reveal that the polymersomes are stable under the reaction conditions. The polymer-filled nanoreactors mimic the membrane and cytosol of cells and can be useful tools to study enzymatic behavior in crowded macromolecular environments.

Optically responsive supramolecular polymer glasses.

The reversible and dynamic nature of non-covalent interactions between the constituting building blocks renders many supramolecular polymers stimuli-responsive. This was previously exploited to create thermally and optically healable polymers, but it proved challenging to achieve high stiffness and good healability. Here we present a glass-forming supramolecular material that is based on a trifunctional low-molecular-weight monomer ((UPyU)3TMP). Carrying three ureido-4-pyrimidinone (UPy) groups, (UPyU)3TMP forms a dynamic supramolecular polymer network, whose properties are governed by its cross-linked architecture and the large content of the binding motif. This design promotes the formation of a disordered glass, which, in spite of the low molecular weight of the building block, displays typical polymeric behaviour. The material exhibits a high stiffness and offers excellent coating and adhesive properties. On account of reversible dissociation and the formation of a low-viscosity liquid upon irradiation with ultraviolet light, rapid optical healing as well as (de)bonding on demand is possible.

Luminescent nanoparticles with lanthanide-containing poly(ethylene glycol)-Poly(ε-caprolactone) block copolymers.

Lanthanide-containing nanoparticles have attracted much attention due to their unique optical properties and potential in nanotechnological applications. An amphiphilic block copolymer of poly(ethylene glycol)-b-poly(ε-caprolactone) methyl ether (mPEG-PCL) was functionalized with a dipicolinic acid (dpa) moiety and coordinated to lanthanide ions to afford [Ln(dpa-PCL-PEG-OCH3)3](HNEt3)3 (Ln = Eu(3+), Tb(3+)). Micelle-like nanoparticles of dpa-PCL-PEG-OCH3 macroligand and metal-centered polymers were prepared by solvent displacement methods. Dynamic light scattering analysis (DLS) and cryogenic transmission electron microscopy images confirmed the presence of solid sphere (<47 nm in diameter) and vesicle (>47 nm in diameter) morphologies. The viability and stability of the lanthanide complexes in micelle-like nanoparticles was explored by DLS and luminescence spectroscopy, and found to be stable for several weeks.

Magnetoliposomes: opportunities and challenges

Abstract Combining liposomes with magnetic nanoparticles is an intriguing approach to create multifunctional vesicles for medical applications, which range from controlled drug delivery vehicles to diagnostic imaging enhancers. Over the past decade, significant effort has been invested in developing such hybrids – widely known as magnetoliposomes – and has led to numerous new concepts. This review provides an overview on of the current state of the art in this field. The concept of magnetic fluid hyperthermia and stimuli-responsive nanoparticles for drug delivery is briefly recapitulated. The materials needed for these hybrids are addressed as well. The three typically followed approaches to associate magnetic nanoparticles to the liposomes are described and discussed more in detail. The final chapters are dedicated to the analytical methods used to characterize these hybrids and to theoretical considerations relevant for bilayer-embedded nanoparticles.

A lock-in-based method to examine the thermal signatures of magnetic nanoparticles in the liquid, solid and aggregated states

We propose a new methodology based on lock-in thermography to study and quantify the heating power of magnetic nanoparticles. Superparamagnetic iron oxide nanoparticles exposed to a modulated alternating magnetic field were used as model materials to demonstrate the potency of the system. Both quantitative and qualitative information on their respective heating power was extracted at high thermal resolutions under increasingly complex conditions, including nanoparticles in the liquid, solid and aggregated states. Compared to conventional techniques, this approach offers a fast, sensitive and non-intrusive alternative to investigate multiple and dilute specimens simultaneously, which is essential for optimizing and accelerating screening procedures and comparative studies.

Mimicking the chemistry of natural eumelanin synthesis: the KE sequence in polypeptides and in proteins allows for a specific control of nanosized functional polydopamine formation

The oxidation of dopamine and of other catecholamines leads to the formation of conformal films on the surface of all known materials and to the formation of a precipitate in solution. In some cases, it has been shown that the addition of additives in the dopamine solution, like certain surfactants or polymers, polyelectrolytes, and certain proteins, allows to get polydopamine nanoparticles of controlled size and the concomitant decrease, in an additive/dopamine dependent manner, in film formation on the surface of the reaction beaker. However, the mechanism behind this controlled oxidation and self-assembly of catecholamines is not known. In this article, it is shown that a specific diad of amino acids in proteins, namely KE, allows for specific control in the oxidation-self-assembly of dopamine to obtain polydopamine@protein core-shell nanoparticles which are biocompatible. The interactions between dopamine and the adjacent KE amino acids potentially responsible for the size control of polydopamine aggregates was investigated by molecular dynamics simulations. The obtained core-shell nanoparticles display the biological activity of the protein used to control the self-assembly of PDA. The photon to heat conversion ability of PDA is conserved in the PDA@protein particles.

Assessing the Stability of Fluorescently Encoded Nanoparticles in Lysosomes by Using Complementary Methods

Nanoparticles (NPs) are promising tools in biomedical research. In vitro testing is still the first method for initial evaluation, however, NP colloidal behavior and integrity, in particular inside cells (i.e. in lysosomes), are largely unknown and difficult to evaluate due to the complexity of the environment. Furthermore, while the majority of NPs are usually labelled with fluorescent dyes for tracking purposes, the effect of the lysosomal environment on the fluorophore properties, as well as the ensuing effects on data interpretation, is often only sparsely addressed. In this work, we have employed several complementary analytical methods to better understand the fate of fluorescently encoded NPs and identify potential pitfalls that may arise from focusing primary analysis on one single attribute, e.g. fluorophore detection. Our study shows that in a lysosomal environment NPs can undergo significant changes resulting in dye quenching and distorted fluorescence signals.