USPIO size control through microwave nonaqueous sol-gel method for neoangiogenesis T2 MRI contrast agent.

AIM: Tunable size ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles from 3 to 9 nm coated with polyethylene glycol phosphonate moieties have been designed for neovascularization MRI. MATERIALS & METHODS: USPIO were synthesized using a nonaqueous sol-gel method. An ischemia-reperfusion rat model has been chosen for neo-angiogenesis and scanned on MRI after injection of different sized USPIO. Histological studies have been performed for USPIO localization within the tissue. RESULTS: The magnetic properties and consequently their MRI relaxivities are drastically dependent on the crystalline core size. In vivo MRI spots were observed specifically in the ischemic area. The best MRI contrast within neovascularization is generated by 6 nm nanoparticles proving that compromise between T2 relaxivity and physico-chemical properties is essential for the design of effective MRI contrast agent.

In silico studies, synthesis and binding evaluation of substituted 2-pyrrolidinones as peptidomimetics of RGD tripeptide sequence.

In silico optimisation, synthesis and binding evaluation of αvß3 integrin's affinity for precursors of a new RGD peptidomimetics family are presented. The 2-pyrrolidinone building block was obtained by condensation of l-lysine with dimethoxydihydrofuran followed by reduction. The ring was functionalized with a carboxylic acid and a guanidinium appendage. On the pyrrolidinone heterocycle, the effects on affinity of position, length and relative geometry of the two acid or basic functionalized side chains introduced on the pyrrolidinone ring have been previously evaluated by docking studies. Peptidomimetics have finally been evaluated by competition binding assays for αvß3 integrin's affinity using radio-ligands.

Carbodiimide versus click chemistry for nanoparticle surface functionalization: a comparative study for the elaboration of multimodal superparamagnetic nanoparticles targeting αvß3 integrins.

Superparamagnetic fluorescent nanoparticles targeting αvß3 integrins were elaborated using two methodologies: carbodiimide coupling and click chemistries (CuACC and thiol-yne). The nanoparticles are first functionalized with hydroxymethylenebisphonates (HMBP) bearing carboxylic acid or alkyne functions. Then, a large number of these reactives functions were used for the covalent coupling of dyes, poly(ethylene glycol) (PEG), and cyclic RGD. Several methods were used to characterize the nanoparticle surface functionalization, and the magnetic properties of these contrast agents were studied using a 1.5 T clinical MRI. The affinity toward integrins was evidenced by solid-phase receptor-binding assay. In addition to their chemoselective natures, click reactions were shown to be far more efficient than the carbodiimide coupling. The grafting increase was shown to enhance targeting affinity to integrin without imparing MRI and fluorescent properties.

Optimized multimodal nanoplatforms for targeting α(v)ß3 integrins.

Magnetic Resonance Imaging (MRI) using contrast agents is a very powerful technique for diagnosis in clinical medicine and biomedical research. The synthesis of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles targeting αvß3 integrins and acting as new MRI contrast agents seems to be a promising way for cancer diagnosis. Indeed, it is well established that αvß3 integrin plays a key role in tumor angiogenesis acting like a receptor for the extracellular matrix proteins like vitronectin, fibronectin through the arginine-glycine-aspartic acid (RGD) sequence. Up-regulation of αvß3 has been found to be associated with a wide range of cancers, making it a broad-spectrum tumor-marker. In this study, USPIO nanocrystals were synthesized and surface passivated with caffeic acid. The large number of the carboxylic acid functions at the outer surface of the nanoplatforms was used for the covalent coupling of Rhodamine123, polyethylene glycol (PEG) and cyclic RGD. Soluble carbodiimide (EDC) and N-hydroxysuccinimide (NHS) were used to crosslink carboxylic acid with the amino group of the ligands. We examined the design of the nanoplatforms with each individual entity and then the combination of two and three of them. Several methods were used to characterize the nanoparticle surface functionalization and the magnetic properties of these contrast agents were studied using a 1.5 T clinical MRI scanner. The affinity towards integrins was evidenced by surface plasmon resonance and solid-phase receptor-binding assay.