Theranostic gadolinium-based nanoparticles AGuIX®: in vivo imaging and safety evaluation
International audience; IntroductionA new efficient type of gadolinium (Gd)-based theranostic agent (AGuIX®) has recently been developed for MRI-guided radiotherapy.1 These nanoparticles consist of a polysiloxane network surrounded by Gd chelates. Nanoparticles, which contain high-Z contrast agents such as Gd-based nanoparticles, increase the sensitivity of the tumor to radiation. Owing to their small size (3 +/- 0.1 nm), AGuIX® typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes.2 Multi-imaging properties and safety evaluation of the Gd-based nanoparticles have been investigated before their clinical transfer. MethodsGd-based nanoparticles have …
Aza-BODIPY: A New Vector for Enhanced Theranostic Boron Neutron Capture Therapy Applications
Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on the nuclear capture of slow neutrons by stable 10B atoms followed by charged particle emission that inducing extensive damage on a very localized level (<
Near-infrared emitting fluorescent homobimetallic gold(I) complexes displaying promising in vitro and in vivo therapeutic properties
International audience; Boron neutron capture therapy (BNCT) has the potential to specifically destroy tumor cells without damaging the tissues infiltrated by the tumor. BNCT is a binary treatment method based on the combination of two agents that have no effect when applied individually: 10B and thermal neutrons. Exclusively, the combination of both produces an effect, whose extent depends on the amount of 10B in the tumor but also on the organs at risk. It is not yet possible to determine the 10B concentration in a specific tissue using non-invasive methods. At present, it is only possible to measure the 10B concentration in blood and to estimate the boron concentration in tissues based o…
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…
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.
Bax-derived membrane-active peptides act as potent and direct inducers of apoptosis in cancer cells.
SUMMARYAlthough many cancer cells are primed for apoptosis, they usually develop resistance to cell death at multiple levels. Permeabilization of the outer mitochondrial membrane, which is mediated by proapoptotic Bcl-2 family members like Bax, is considered as a point-of-no-return for initiating apoptotic cell death. This crucial role has placed Bcl-2 family proteins as recurrent targets for anticancer drug development. Here, we propose and demonstrate a new concept based on using minimal active version of Bax to induce cell death independently of endogenous Bcl-2 proteins. We show that membrane-active segments of Bax can directly induce the release of mitochondria-residing apoptogenic fac…
Water-Soluble Aza-BODIPYs: Biocompatible Organic Dyes for High Contrast In Vivo NIR-II Imaging
International audience; A simple NIR-II emitting water-soluble system has been developed and applied in vitro and in vivo. In vitro, the fluorophore quickly accumulated in 2D and 3D cell cultures and rapidly reached the tumor in rodents, showing high NIR-II contrast for up to 1 week. This very efficient probe possesses all the qualities necessary for translation to the clinic as well as for the development of NIR-II emitting materials.
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…