Design of reversibly disulfide core cross-linked polymer micelles

Poster (2011, November 21)

Over the last decade, polymer micelles attracted an increasing interest in drug pharmaceutical research because they could be used as efficient drug delivery systems. Micelles of amphiphilic block ... [more ▼]

Over the last decade, polymer micelles attracted an increasing interest in drug pharmaceutical research because they could be used as efficient drug delivery systems. Micelles of amphiphilic block copolymers are supramolecular core-shell type assemblies of tens of nanometers in diameter. An accumulation of polymer nanocarriers to solid tumours is possible due to the EPR effect. Even if micelles get a high stability in aqueous media, the dissociation of micelles is not always preserved when they are injected in the blood compartment. This work aims at reporting on the design of reversibly cross-linked micelles based on PEO-b-PCL copolymers by introducing disulfide bridges in the micelle core to provide higher stability. Different kinds of macromolecular architectures are employed to study their impact on the micelles and their biological behavior. These new functional copolymers were all successfully micellized, reversibly cross-linked and are stealthy, which show the efficiency of the developed cross-linking process and offer a set of nanocarriers to be tested further, as shown on the first biological tests. [less ▲]

Stealth macromolecular platforms for the design of MRI blood pool contrast agents

in Polymer Chemistry (2011), 2(10), 2316-2327

Stealth macromolecular platforms bearing alkyne groups and poly(ethylene oxide) brushes were synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization. The anchoring of Gd3 ... [more ▼]

Stealth macromolecular platforms bearing alkyne groups and poly(ethylene oxide) brushes were synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization. The anchoring of Gd3+-chelates bearing an azide group was then carried out by the Huisgen 1,3-dipolar cycloaddition (“click”) reaction in mild conditions, leading to macrocontrast agents for MRI applications. The gadolinium complex is hidden in the PEO shell that renders the macrocontrast agents free of any cytotoxicity and stealth to proteins of the immune system. Relaxometry measurements have evidenced an improved relaxivity of the macrocontrast agent compared to ungrafted gadolinium chelate. Moreover, this relaxivity is further enhanced when the spacer length between the Gd3+-chelate and the polymer backbone is shorter, as the result of its decreased tumbling rate. These novel products are therefore promising candidates for MRI applications. [less ▲]

Convenient grafting through approach for the preparation of stealth polymeric blood pool magnetic resonance imaging contrast agents

in Journal of Polymer Science. Part A-1, Polymer Chemistry (2011), 49(17), 3700-3708

New hydrosoluble magnetic resonance imaging (MRI) macrocontrast agents are synthesized by reversible addition fragmentation chain transfer (RAFT) copolymerization of poly(ethylene oxide) methyl ether ... [more ▼]

New hydrosoluble magnetic resonance imaging (MRI) macrocontrast agents are synthesized by reversible addition fragmentation chain transfer (RAFT) copolymerization of poly(ethylene oxide) methyl ether acrylate (PEOMA) with an acrylamide bearing a ligand for gadolinium, followed by the complexation of Gd3+. This convenient and simple grafting through approach leads to macrocontrast agents with a high relaxivity at high frequency that is imparted by the restricted tumbling of the Gd3+ complex caused by its attachment to the polymer backbone. Importantly a very low protein adsorption is also evidenced by the hemolytic CH50 test. It is the result of the poly(ethylene oxide) (PEO) brush that efficiently hides the gadolinium complex and renders it stealth to the proteins of the immune system. Improved contrast and long blood circulating properties are thus expected for these macrocontrast agents. [less ▲]

Poly(vinyl alcohol)-containing nanohydrids for biomedical applications

Poster (2011, June 13)

Synthesis and characterization of reversibly core cross-linked micelles sensitive to reductive environment

Poster (2011, May 12)

Design and characterization of novel stealth Gd(II)-DOTA conjugates for magnetic resonance inaging (MRI)

Poster (2010, November 29)

Polymer micelles decorated by gadolinium complexes as MRI blood contrast agents: design, synthesis and properties

in Polymer Chemistry (2010), 1

New micellar macrocontrast agents with improved contrast at high frequencies were designed by grafting a gadolinium based contrast agent onto functional stealth micelles formed by poly(ethylene oxide)-b ... [more ▼]

New micellar macrocontrast agents with improved contrast at high frequencies were designed by grafting a gadolinium based contrast agent onto functional stealth micelles formed by poly(ethylene oxide)-b-poly(ε-caprolactone) (PEO-b-PCL) in water. As evidenced by relaxometry measurements and the hemolytic CH50 test, the new contrast agents are of interest as MRI blood pool agents. [less ▲]

pH-responsive flower-type micelles formed by a biotinylated poly(2-vinylpyridine)-block-poly(ethylene-oxide)-block-poly(ε-caprolactone) triblock copolymer

in Advanced Functional Materials (2009), 19(9), 1416-1425

In the present work, a method is proposed to assemble pH-responsive, flower-like micelles that can expose a targeting unit at their periphery upon a decrease in pH. The micelles are composed of a novel ... [more ▼]

In the present work, a method is proposed to assemble pH-responsive, flower-like micelles that can expose a targeting unit at their periphery upon a decrease in pH. The micelles are composed of a novel biotinylated triblock copolymer of poly(-caprolactone)-block-poly(ethylene oxide)-block-poly(2-vinylpyridine) (PCL-b-PEO-b-P2VP) and the non-biotinylated analogue. The block copolymers are synthesized by sequential anionic and ring-opening polymerization. The pH-dependent micellization behaviour in aqueous solution of the triblock copolymers developed is studied using dynamic light scattering, zeta potential, transmission electron microscopy (TEM), and fluorimetric measurements. The shielding of the biotin at neutral pH and their availability at the micelle surface upon protonation is established by TEM and surface plasmon resonance with avidin and streptavidin-coated gold surfaces. The preliminary stealthy behavior of these pH-responsive micelles is examined using the complement activation (CH50) test. [less ▲]

PEO coated magnetic nanoparticles for biomedical application

in European Polymer Journal (2008), 44(10), 3191-3199

This paper reports on the preparation, characterization and stealthiness of superparamagnetic nanoparticles (magnetite Fe3O4) with a 5 nm diameter and stabilized in water (pH 6.5) by a shell of water ... [more ▼]

This paper reports on the preparation, characterization and stealthiness of superparamagnetic nanoparticles (magnetite Fe3O4) with a 5 nm diameter and stabilized in water (pH 6.5) by a shell of water-soluble poly(ethylene oxide) (PEO) chains. Two types of diblock copolymers, i.e., poly(acrylic acid)-b-poly(ethylene oxide), PAA–PEO, and poly(acrylic acid)-b-poly(acrylate methoxy poly(ethyleneoxide)), PAA–PAMPEO, were prepared as stabilizers with different compositions and molecular weights. At pH 6.5, the negatively ionized PAA block interacts strongly with the positively-charged nanoparticles, thus playing the role of an anchoring block. Aggregates of coated nanoparticles were actually observed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The hydrodynamic diameter was in the 50–100 nm range and the aggregation number (number of nanoparticles per aggregate) was lying between several tens and hundred. Moreover, the stealthiness of these aggregates was assessed “in vitro” by the hemolytic CH50 test. No response of the complement system was observed, such that biomedical applications can be envisioned for these magnetic nanoparticles. Preliminary experiments of magnetic heating (10 kA/m; 108 kHz) were performed and specific absorption rate varied from 2 to 13 W/g(Fe). [less ▲]

Magnetic nanoparticles coated by temperature responsive copolymers for hyperthermia

in Journal of Materials Chemistry (2008), 18(28), 3352-3360

Various temperature-responsive N-isopropylacrylamide-based functional copolymers were prepared and used for the stabilization of iron oxide nanoparticles. The copolymers investigated are poly(acrylic acid ... [more ▼]

Various temperature-responsive N-isopropylacrylamide-based functional copolymers were prepared and used for the stabilization of iron oxide nanoparticles. The copolymers investigated are poly(acrylic acid)-b-poly(N-isopropylacrylamide) (PAA-PNIPAM) and poly(acrylic acid)-b-poly(N-isopropylacrylamide)-b-poly(acrylate methoxy poly(ethylene oxide)) (PAA-PNIPAM-PAMPEO), with different molecular weights. The coated nanoparticles were characterized in terms of size by a combination of dynamic light scattering (DLS) and transmission electron microscopy (TEM). A sharp temperature transition was confirmed by particle size measurements vs. temperature. In addition, the stealthiness of the coated nanoparticles has been assessed in vitro by the haemolytic CH50 test. These measurements evidenced the crucial role of the PEO segments on the stealthiness of the nanoparticles and thus that such copolymers are particularly suitable for biomedical applications. Preliminary experiments of alternating magnetic field induced heating were performed and specific absorption rates of the various samples were recorded. [less ▲]