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Encapsulation / vectorisation

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Photocontrol of luminescent inorganic nanocrystals via an organic molecular switch

A photo-controlled and quasi-reversible switch of the luminescence of hexadecylamine-coated ZnO nanocrystals (ZnO@HDA Ncs) is operated via a molecular photoswitch (dithienylethene, DTE). The interaction between the DTE switch and the ZnO@HDA Ncs is thoroughly investigated using NMR spectroscopy techniques, including DOSY and NOESY, showing that the DTE switch is weakly adsorbed at the surface of the Ncs through the formation of hydrogen bonds with HDA. Steady state and time-resolved luminescence quenching experiments show a complex behavior, related to the spatial distribution of the emitting defects in the Ncs. Analysis of the data using models previously developed for Ncs supports static quenching. Both isomeric forms (open or closed) of the DTE switch quench the emission of Ncs, the efficiency being more than ten times higher for the closed isomer. The mechanism of quenching is discussed and we show that quenching occurs mainly through resonant energy transfer for the closed isomer and through electron transfer for the open one. The HDA layer mediates the quenching efficiency as only defects located near the surface are quenched.

J. Massaad, Y. Coppel, M. Sliwa, M. L. Kahn, C. Coudret, F. Gauffre, Phys.Chem.Chem.Phys. 2014, 16, 22775.


Simple Engineering of Polymer–Nanoparticle Hybrid Nanocapsules

A general method to generate hybrid hollow capsules is reported. The process is based on the stabilization of solvent droplets by nanoparticles, in macroscopically miscible mixtures of tetrahydrofuran (THF) and water. After addition of a crosslinking polymer and removal of the solvent core, capsules of diameter ca 100 nm are obtained. This novel strategy does not require the use of block copolymers. In contrast, most methods reporting the formation of hybrid nanocapsules incorporate nanoparticles into block-copolymer polymersomes or use nanoparticles tethered with block-copolymers. The nanocapsules were characterized using a full set of techniques including nanoparticle tracking analysis, electron microscopy and liquid phase atomic force microscopy. Our results show that the vesicular shape of the nanocapsules is templated by the liquid droplets. Nanocapsules were prepared from quantum dots, gold nanoparticles, superparamagnetic iron oxide nanoparticles and mixtures of particles. The entrapment of a fluorescent dye was also demonstrated. Thus, nanocapsules with dual properties (e.g., magnetic and fluorescent) are easily obtained. Interestingly, the magnetic nanocapsules enable magnetic resonance imaging contrast enhancement of tumors in vivo.

F. Sciortino, G. Casterou, P.-A. Eliat, M.-B. Troadec, C. Gaillard, S. Chevance, M. L. Kahn, F. Gauffre, ChemNanoMat 2016, 2, 796.


Direct and one-pot conversion of polyguluronates and alginates into alkyl-L-guluronamide-based surfactant compositions

We describe here an efficient one-pot process for the synthesis of 100% bio-based L-guluronic acid based surfactant compositions as emulsion stabilizers, directly from L-polyguluronate or whole alginate, a renewable polysaccharide extracted from brown seaweeds. The transformation of these polymers into long-chain alkyl-L-guluronamides associated with D-mannuronamides when the alginate was used, has been achieved through the preparation of n-butyl uronate monosaccharide intermediates involving methane sulfonic acid-promoted hydrolysis, Fisher glycosylation and esterification reactions, followed by an in situ solvent-free aminolysis reaction with fatty amines.

N. Sari-Chmayssem, F. Pessel, J.-P. Guégan, S. Taha, H. Mawlawic, T. Benvegnu, Green Chem., 2016, 18, 6573.


Folate-conjugated stealth archaeosomes for the targeted delivery of novel antitumoral peptides

In this work, novel archaeosomes based on Egg-PC and a mixture of PEGylated archaeal tetraether lipids were investigated as nanocarriers for in vitro delivery of an original anticancer peptide. With the aim to develop site-specific drug targeting, a tetraether equipped with a folate ligand at the PEG5000 terminal end (FA–PEG5000–tetraether) was synthesized in order to bind to folate receptors (over)expressed on the tumor cell surfaces. The original peptide A1 and its inactive analogue A1Yala (17 amino acids) were encapsulated into Egg-PC vesicles incorporating FA–PEG5000–tetraether and/or PEG2000–tetraether lipids in order to evaluate the in vitro anticancer activity of A1-loaded archaeosomes. Results showed a particular behaviour when A1 was encapsulated into the folate-equipped archaeosomes particularly during the first hour of incubation.

A. Jiblaoui, J. Barbeau, T. Vivès, P. Cormier, V. Glippa, B. Cosson, T. Benvegnu, RSC Adv., 2016, 6, 75234.


Optimization of lipase-catalyzed polymerization of benzyl malolactonate through a Design of Experiment (DoE) approach.

Polyesters are polymers of choice in the design of drug delivery systems as a result of their good biocompatibility and their (bio)degradability. Such polyesters are mainly obtained by polymerization techniques using chemically-based initiators whose presence in the final materials, even at trace levels, might induce toxic effects upon in vivo uses. Therefore, lipases-catalyzed ring opening polymerization (ROP) of lactones might be considered as interesting solutions. In this context, we have studied the possibilities to use lipase-catalyzed ROP of the benzyl malolactonate (MLABe) to obtain the poly(benzyl malate), PMLABe. A Design of Experiment (DoE) approach has been elaborated in order to identify the important parameters having a significant influence on the polymerization reaction and on the characteristics of the obtained PMLABe. Such DoE technique allowed us to select conditions for lipase-catalyzed ROP of MLABe leading to PMLABe with a mass-average molar mass of around 10,000 g/mol with a dispersity of 1.4.

H. Casajus, S. Tranchimand, D. Wolbert,C. Nugier-Chauvin, S. Cammas-Marion, J. Appl. Polym. Sci., 2017, doi: 10.1002/app.44604.


In vitro Toxicity Evaluation and in vivo Biodistribution of Polymeric Micelles Derived from Poly(ethylene glycol)-b-poly(benzylmalate) Copolymers

The development of polymeric micelles for site-specific drug delivery is an exponentially growing field of research. In this context, we have designed two degradable amphiphilic copolymers, the poly(ethylene glycol)-b-poly(benzyl malate) (PEG42-b-PMLABe73) and the biotin-poly(ethylene glycol)-b-poly(benzyl malate) (Biot-PEG62-b-PMLABe73). The copolymer bearing biotin residue was synthesized in order to formulate micelles for grafting biotinylated cyclic RGD peptide onto their surface via the bridging streptavidin.
Our study aimed at investigating the in vitro and in vivo toxicity of such micelles and to evaluate the potential of these nanovectors for hepatocyte-targeted drug delivery. Methods: The toxicity of micelles obtained by the nanoprecipitation method and characterized by dynamic light scattering and zeta potential measurement was evaluated in vitro using the differentiated hepatocyte-like HepaRG cells and in vivo in mice.
The micelles derived from PEG42-b-PMLABe73, Biot-PEG62-b-PMLABe73 and RGDBiot-Strept-Biot-PEG62-b-PMLABe73 did not affect the cell proliferation and apoptotic indexes in HepaRG hepatoma cells and were well tolerated in mice following systemic injection. The hydrophobic fluorescent probes DiD oil and DiR were efficiently encapsulated in PEG-b-PMLABe-derived micelles allowing the visualization of their uptake into HepaRG cells. Furthermore, the addition of RGD peptide onto micelles strongly enhanced the cell uptake in vitro and liver targeting in vivo.
These data demonstrate the low toxicity of poly(benzyl malate) derived copolymers towards hepatocyte-like cells and emphasize their potential use for the design of liver targeting nanovectors.

E. Vene, K. Jarnouen, Z. W. Huang, B. Wahib, T. Montier, S. Cammas-Marion, P. Loyer, Pharm. Nanotechnol. 2016, 4, 24.


Synthesis and characterisation of bio-based polyester materials fromvegetable oil and short to long chain dicarboxylic acids

Polyester-type polymers were efficiently prepared from broccoli seed oil and several carboxylic diacids.The polyesters were prepared through a simple two-step process including oxidation of the insatura-tions to oxiranes followed by ring opening with dicarboxylic acids under basic conditions. Eight polymermaterials derived from different fatty diacids (from 5 C to 16 C) and an aromatic diacid were prepared andcharacterised. Rubber-type crosslinked biobased materials exhibited low Tgvalues comprised between −5 and +5°C depending on the diacid type and length.

M. Gobin, P. Loulergue, J.-L. Audic, L. Lemiègre, Indus. Crops Prod. 2015, 213.


Collapsed bipolar glycolipids at the air/water interface: Effect of the stereochemistry on the stretched/bent conformations

This article describes a comparative study of several bipolar lipids derived from tetraether structures. The sole structural difference between the main two glycolipids is a unique stereochemical variation on a cyclopentyl ring placed in the middle of the lipids. We discuss the comparative results obtained at the air/water interface on the basis of tensiometry and ellipsometry. Langmuir–Blodgett depositions during lipid film compressions and decompressions were also analyzed by AFM. The lactosylated tetraether (bipolar) lipid structures involved the formation of highly stable multilayers, which are still present at 10 mN m-1 during decompression. This study suggests also that the stereochemistry of a central cyclopentyl ring dramatically drives the conformation of the corresponding bipolar lipids. Both isomers (trans and cis) adopt a U-shaped (bent) conformation at the air/water interface but the trans cyclopentyl ring induces a much more frustration within this type of conformation. Consequently, this bipolar lipid (trans-tetraether) undergoes a flip of one polar head-group (lactosyl) leading to a stretched conformation during collapse.

A. Jacquemet, N. Terme, T. Benvegnu, V. Vié, L. Lemiègre, J. Coll. Inter. Sci. 2013, 72.