Multifunctional Gold Nanoparticles for Image-Guided Microbeam Radiation Therapy

International audience; Owing to their large range of properties which can be accurately tuned by the chemical composition, the shape and the dimensions, multifunctional nanoparticles appear as promising candidates for imageguided therapy. For achieving this goal, we developed the synthesis of gold nanoparticles which are designed for combining multimodal imaging (magnetic resonance imaging (MRI), scintigraphy (SPECT), ultrasound imaging (echography) and X-ray imaging) and radiotherapy [1-5]. Ultrasmall gold nanoparticles were synthesized by reducing gold salt in presence of various highly hydrophilic dithiolated polyaminocarboxylate ligands (linear (DTDTPA) and macrocyclic (TADOTA, TADOTAG…

Apparent magic numbers in embedded Ti-O clusters

Stable clusters constituted of four ${\mathrm{TiO}}_{2}$ entities have been evidenced in nanometer-sized spinel oxides by a combination of diffraction and x-ray-absorption experiments. Contrary to free clusters, the size of the embedded clusters is strongly determined by the constraints imposed by the surrounding matrix so that the magic number of four is in fact specific to the matrix and only then apparent.

A top-down synthesis route to ultrasmall multifunctional Gd-based Silica nanoparticles for theranostic applications

International audience; New, ultrasmall nanoparticles with sizes below 5 nm have been obtained. These small rigid platforms (SRP) are composed of a polysiloxane matrix with DOTAGA (1,4,7,10-tetraazacyclododecane-1-glutaric anhydride-4,7,10-triacetic acid)-Gd3+ chelates on their surface. They have been synthesised by an original top-down process: 1) formation of a gadolinium oxide Gd2O3 core, 2) encapsulation in a polysiloxane shell grafted with DOTAGA ligands, 3) dissolution of the gadolinium oxide core due to chelation of Gd3+ by DOTAGA ligands and 4) polysiloxane fragmentation. These nanoparticles have been fully characterised using photon correlation spectroscopy (PCS), transmission elec…

International Society for Therapeutic Ultrasound Conference 2016

Minor changes in the macrocyclic ligands but major consequences on the efficiency of gold nanoparticles designed for radiosensitization

International audience; Many studies have been devoted to adapting the design of gold nanoparticles to efficiently exploit their promising capability to enhance the effects of radiotherapy. In particular, the addition of magnetic resonance imaging modality constitutes an attractive strategy for enhancing the selectivity of radiotherapy since it allows the determination of the most suited delay between the injection of nanoparticles and irradiation. This requires the functionalization of the gold core by an organic shell composed of thiolated gadolinium chelates. The risk of nephrogenic systemic fibrosis induced by the release of gadolinium ions should encourage the use of macrocyclic chelat…

The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy

International audience; A new efficient type of gadolinium-based theranostic agent (AGuIX) has recently been developed for magnetic resonance imaging (MRI)-guided radiotherapy. These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Due to their small size (<5 nm), AGuIX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, while a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, these particles present no evidence of toxicity, in the absence of irradiation with up to 10 times the planned dose f…

Ultrasmall Rigid Particles as Multimodal Probes for Medical Applications

International audience; Ultrasmall but multifunctional: Rigid imaging particles that are smaller than 5 nm in size can be obtained in a top-down process starting from a core–shell structure (core=gadolinium oxide; shell=polysiloxane). They represent the first multifunctional silica-based particles that are sufficiently small to escape hepatic clearance and enable animal imaging by four complementary techniques.

AGuIX® from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine.

International audience; AGuIX® are sub-5 nm nanoparticles made of a polysiloxane matrix and gadolinium chelates. This nanoparticle has been recently accepted in clinical trials in association with radiotherapy. This review will summarize the principal preclinical results that have led to first in man administration. No evidence of toxicity has been observed during regulatory toxicity tests on two animal species (rodents and monkeys). Biodistributions on different animal models have shown passive uptake in tumours due to enhanced permeability and retention effect combined with renal elimination of the nanoparticles after intravenous administration. High radiosensitizing effect has been obser…

Functionalization of ultrasmall nanoparticles for theranosctic applications

International audience

AGuIX modifications for active tumor targeting and radiolabelling

International audience

Radiolabeling for long term biodistribution of ultrasmall nanoparticles designed for radiotherapy guided by MRI

International audience

Functionalization of theranostic AGuIX® nanoparticles for PET/MRI/optical imaging

International audience; A novel trifunctional imaging probe containing a chelator of radiometal for PET, a NIR heptamethine cyanine dye, and a bioconjugatable handle, has been grafted onto AGuIX® nanoparticles via a Michael addition reaction. The resulting functionalized nanoparticles have been fully characterized, radiolabelled with 64Cu, and evaluated in a mice TSA tumor model using multimodal (PET/MRI/optical) imaging.

One-pot direct synthesis for multifunctional ultrasmall hybrid silica nanoparticles

International audience; Ultrasmall silica nanoparticles (NPs), having hydrodynamic diameters under 10 nm are promising inorganic platforms for imaging and therapeutic applications in medicine. Herein is described a new way for synthesizing such kind of NPs in a one-pot scalable protocol. These NPs bear DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) ligands on their surface that can chelate different metals suitable for a wide variety of biomedical applications. By varying the ratio of the precursors, the hydrodynamic diameters of the particles can be controlled over the range of 3 to 15 nm. The resulting NPs have been characterized extensively by complementary techniques li…

X-ray induced PDT and scintillating particles

International audience

Ultrasmall particles for Gd-MRI and68Ga-PET dual imaging

Nanoparticles made of a polysiloxane matrix and surrounded by 1,4,7,10-tetraazacyclododecane-1-glutaric anhydride-4,7,10-triacetic acid (DOTAGA)[Gd(3+) ] and 2,2'-(7-(1-carboxy-4-((2,5-dioxopyrrolidin-1-yl)oxy)-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid) NODAGA[(68) Ga(3+) ] have been synthesized for positron emission tomography/magnetic resonance (PET/MRI) dual imaging. Characterizations were carried out in order to determine the nature of the ligands available for radiolabelling and to quantify them. High radiolabelling purity (>95%) after (68) Ga labelling was obtained. The MR and PET images demonstrate the possibility of using the nanoparticles for a combined PET/MR imaging sca…