Easy reversible clustering of gold nanoparticles via pH-Induced assembly of PVP-b-PAA copolymer.

The growing demand of novel hybrid organic/inorganic systems with exciting properties has contributed to an increasing need for simplifying production strategies. Here, we report a simple method to obtain controlled three-dimensional hybrid architectures, in particular hybrid supracolloids (hSC), formed by gold nanoparticles and a double hydrophilic block copolymer, specifically the poly(acrylic acid)-block-poly(N-vinyl-2-pyrrolidone) (PAA-b-PVP), directly in aqueous medium. The ubiquitous pH-sensitive poly(acrylic acid) (PAA) block initiates the assembly through pH changes, while the poly(N-vinyl-2-pyrrolidone) block assures the close affinity with the AuNPs. We demonstrate that the formation of hybrid supracolloids (hSC) is the result of the synergetic behavior of the two specific polymeric blocks. Additionally, the entire process shows spontaneous and fast switchability. The nanostructured copolymer behaves like a highly swollen hydrogel and displays a disordered internal structure. The driving force for the association of the copolymer chains is induced by the synergetic effects of the decrease in solubility of the poly(acrylic acid) block and the formation of inter and intra chains hydrogen bonds. These were demonstrated by using small angle X-ray scattering (SAXS), quartz crystal microbalance with dissipation monitoring (QCM-D) and scanning transmission electron microscopy coupled with energy-dispersive X-ray spectroscopy (STEM-EDX). In turn, the AuNPs are randomly spread all over the polymeric matrix, as demonstrated by field emission gun - scanning electron microscopy (FEG-SEM). A correlation analysis reveals the hSC density depends mostly on the initial concentration of AuNPs. These results can inspire the fabrication of more complex structures with multicomponent composition.

Simple hybrid polymeric nanostructures encapsulating macro-cyclic Gd/Eu based complexes: luminescence properties and application as MRI contrast agent.

Lanthanide-based macrocycles are successfully incorporated into hybrid polyionic complexes, formed by adding a mixture of zirconium ions to a solution of a double-hydrophilic block copolymer. The resulting nanoobjects with an average radius of approximately 10-15 nm present good colloidal and chemical stability in physiological media even in the presence of competing ions such as phosphate or calcium ions. The final optical and magnetic properties of these objects benefit from both their colloidal nature and the specific properties of the complexes. Hence these new nanocarriers exhibit enhanced T1 MRI contrast, when administered intravenously to mice.

Assemblies of poly(N-vinyl-2-pyrrolidone)-based double hydrophilic block copolymers triggered by lanthanide ions: characterization and evaluation of their properties as MRI contrast agents.

Because of the formation of specific antibodies to poly(ethylene glycol) (PEG) leading to life-threatening side effects, there is an increasing need to develop alternatives to treatments and diagnostic methods based on PEGylated copolymers. Block copolymers comprising a poly(N-vinyl-2-pyrrolidone) (PVP) segment can be used for the design of such vectors without any PEG block. As an example, a poly(acrylic acid)-block-poly(N-vinyl-2-pyrrolidone) (PAA-b-PVP) copolymer with controlled composition and molar mass is synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. Mixing this copolymer with lanthanide cations (Gd3+, Eu3+, Y3+) leads to the formation of hybrid polyion complexes with increased stability, preventing the lanthanide cytotoxicity and in vitro cell penetration. These new nanocarriers exhibit enhanced T1 MRI contrast, when intravenously administered into mice. No leaching of gadolinium ions is detected from such hybrid complexes.

Hybrid polymeric micelles stabilized by gallium ions: Structural investigation.

The addition of gallium ions to a solution of a double-hydrophilic block copolymer, i.e. poly(ethylene oxide)-block-poly(acrylic acid), leads to the spontaneous formation of highly monodisperse micelles with a Hybrid PolyIon Complexes (HPICs) core. By combining several techniques, a precise description of the HPIC architecture was achieved. In particular and for the first time, NMR and anomalous small angle X-ray scattering (ASAXS) enable tracking of the inorganic ions in solution and highlighting the co-localization of the gallium and the poly(acrylic acid) blocks in a rigid structure at the core of the micelle. Such a core has a radius of ca 4.3 nm while the complete nano-object with its poly(ethylene oxide) shell has a total radius of ca 11 nm. The aggregation number was also estimated using the ASAXS results. This comprehensive structural characterization of the Ga HPICs corroborates the assumptions made for HPICs based on other inorganic ions and demonstrates the universality of the HPIC structure leading, for example, to new families of contrast agents in medical imaging.

Easy colorimetric detection of gadolinium ions based on gold nanoparticles: key role of phosphine-sulfonate ligands.

The possibility to easily and rapidly assess the presence of Gd3+ ions in solution is of paramount importance in many domains like magnetic resonance imaging. In that context, the use of easy to implement colorimetric sensing probes based on gold nanoparticles (AuNPs) is of special interest. Herein, AuNPs functionalized with a commercial bis(p-sulfonatophenyl)phenyl phosphine ligand (BSPP) (AuNP@BSPP), bearing negatively charged sulfonate groups are used as a colorimetric sensing probe. The addition of Gd3+ ions onto these NPs was studied through UV-visible absorbance measurements, Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) and transmission electron microscopy and compared with citrate covered AuNPs. We evidenced interactions between the Gd3+ ions and their water rich coordination sphere and sulfonate groups on the surface of AuNP@BSPP via electrostatic interactions and hydrogen bonding. These interactions induce the reversible aggregation of AuNP@BSPP in the presence of concentrations of Gd3+ ions at a µM level. We took advantage of this phenomenon to develop a simple and fast bench colorimetric assay for the detection of free Gd3+ ions, based on the determination of a flocculation parameter thanks to UV-visible measurements. Limits of detection and quantification were found equal to 0.74 µM and 4.76 µM of Gd3+ ions, respectively, with a high sensitivity that competes with conventional methods used for lanthanide detection.

Gadolinium-based contrast agents: From gadolinium complexes to colloidal systems.

Nowadays, most of the clinically used contrast agents are based on the use of gadolinium molecular complexes like Dotarem®, Magnevist®…. Nevertheless, developing new gadolinium based contrast agents with enhanced relaxivity properties while avoiding gadolinium release in human tissue is still of paramount importance. We describe here two promising families of contrast agents which meets these criteria and compared their properties to the ones of clinically used Gd complexes. The first one is based on contrast agents obtained by covalent or non-covalent interactions of gadolinium molecular complexes with polymers, nanoparticles or liposomes. The second family is based on the formation of gadolinium particles (Gd2O3, GdPO4, NaGdF4, GdF3…) of controlled morphology and composition. The performance of these two families is described as well as their development perspective.