Pentafluorophenyl Ester-based Polymersomes as Nanosized Drug-Delivery Vehicles

In this work, activated ester chemistry is employed to synthesize biocompatible and readily functionalizable polymersomes. Via aminolysis of pentafluorophenyl methacrylate-based precursor polymers, an N-(2-hydroxypropyl) methacrylamide (HPMA)-analog hydrophilic block is obtained. The precursor polymers can be versatile functionalized by simple addition of suitable primary amines during aminolysis as demonstrated using a fluorescent dye. Vesicle formation is proven by cryoTEM and light scattering. High encapsulation efficiencies for hydrophilic cargo like siRNA are achieved using dual centrifugation and safe encapsulation is demonstrated by gel electrophoresis. In vitro studies reveal low cy…

Poly(N-isopropylacrylamide)-Modified Styrene-Butadiene Rubber as Thermoresponsive Material

PeptoSomes for Vaccination: Combining Antigen and Adjuvant in Polypept(o)ide-Based Polymersomes.

In this work, the first vaccine is reported based on a PeptoSome, which contains a model antigen (SIINFEKL) and adjuvant (CpG). PeptoSomes are polypept(o)ide-based polymersomes built of a block-copolymer with polysarcosine (PSar) as the hydrophilic block (X n = 111) and poly(benzyl-glutamic acid) (PGlu(OBn)) as the hydrophobic one (X n = 46). The polypept(o)ide is obtained with low dispersity index of 1.32 by controlled ring-opening polymerization. Vesicle formation by dual centrifugation technique allows for loading of vesicles up to 40 mol%. PeptoSomes are characterized by multiangle dynamic light scattering, static light scattering, and cryogenic transmission electron microscopy (cryoTEM…

Functionalization of Active Ester-Based Polymersomes for Enhanced Cell Uptake and Stimuli-Responsive Cargo Release

Poly(2,3-dihydroxypropyl methacrylamide) (P(DHPMA))-based amphiphilic block copolymers have recently proven to form polymer vesicles (polymersomes). In this work, we further expand their potential by incorporating (i) units for pH-dependent disintegration into the hydrophobic membrane and (ii) mannose as targeting unit into the hydrophilic block. This last step relies on the use of an active ester prepolymer. We confirm the stability of the polymersomes against detergents like Triton X-100 and their low cytotoxicity. The incorporation of 2-(2,2-dimethyl-1,3-dioxolane-4-yl)ethyl methacrylate into the hydrophobic block (lauryl methacrylate) allows a pH-responsive disintegration for cargo rele…

Synthesis of Functional Block Copolymers Carrying One Poly(p-phenylenevinylene) and One Nonconjugated Block in a Facile One-Pot Procedure

Block copolymers composed of a MEH–PPV block and a nonconjugated functional block (molecular weights between 5 and 90 kg/mol) were synthesized in a facile one-pot procedure via ROMP. This one-pot procedure permits the synthesis of numerous block copolymers with little effort. Amphiphilic block copolymers were obtained via incorporation of oxanorbornene carrying a PEG side chain as well as via postpolymerization modification of a reactive ester carrying norbornene derivative with methoxypoly(ethylene glycol)amine. These amphiphilic block copolymers can be self-assembled into micelles exhibiting different sizes (60–95 nm), morphologies (micelles or fused, caterpillar-like micelles), and optic…

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

International audience; We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68…

From Polymers to Nanomedicines: New Materials for Future Vaccines

Nanomedicine is the medical application of nanotechnology and therefore covers various kinds of nanoparticles. In this chapter, we would like to provide a brief introduction and overview of nanoparticles for the modulation of the immune system. In general, these nano-sized objects can be inorganic colloids, organic colloids (synthesized by emulsion polymerization or mini-/nanoemulsion techniques), polymeric aggregates (micelles or polymersomes), core cross-linked aggregates (nanohydrogels, crosslinked micelles, or polyplexes), multifunctional polymer coils, dendritic polymers or perfect dendrimers. A special focus is set on polymeric materials, because the chemical composition of the partic…

Polysarcosine-Based Lipids: From Lipopolypeptoid Micelles to Stealth-Like Lipids in Langmuir Blodgett Monolayers.

Amphiphiles and, in particular, PEGylated lipids or alkyl ethers represent an important class of non-ionic surfactants and have become key ingredients for long-circulating (“stealth”) liposomes. While poly-(ethylene glycol) (PEG) can be considered the gold standard for stealth-like materials, it is known to be neither a bio-based nor biodegradable material. In contrast to PEG, polysarcosine (PSar) is based on the endogenous amino acid sarcosine (N-methylated glycine), but has also demonstrated stealth-like properties in vitro, as well as in vivo. In this respect, we report on the synthesis and characterization of polysarcosine based lipids with C14 and C18 hydrocarbon chains and their end g…