Chemical and in vitro characterizations of a promising bimodal AGuIX probe able to target apoptotic cells for applications in MRI and optical imaging

Abstract

Different studies on AGuIX nanoparticles have been achieved in the biomedical domain, showing that they allow us to combine multimodal and theranostic properties in oncology. The targeting of apoptotic cells presents a wide range of biomedical applications, including the monitoring of antitumoral therapy and the diagnosis of diseases related to this process, such as atherosclerosis, ischemia, chronic inflammation or autoimmune disorders. AGuIX nanoparticles functionalized with a peptide that recognizes apoptotic cells and with organic fluorophores were characterized by several physicochemical and biological methods such as HPLC, relaxometry and photon correlation spectroscopy, which attested to their potential as bimodal tracers detected by optical imaging and MRI. An increase of relaxivity and stability of AGuIX nanoparticles is also observed after their vectorization. The biological efficiency of this novel bimodal probe to target apoptotic cells was evaluated by fluorescence microscopy, relaxometry, MRI and flow cytometry on a lymphoblastic human T-cell line. In vitro cell apoptosis was chemically induced by incubation with camptothecin. Our in vitro experiments showed a significant specificity of vectorized AGuIX nanoparticles for camptothecin-treated cells that suggests their potential efficiency as probes to target apoptosis. Copyright © 2016 John Wiley & Sons, Ltd.

Biodegradation of metal-based ultra-small nanoparticles: A combined approach using TDA-ICP-MS and CE-ICP-MS

“…At tinc=0, the hydrodynamic size of the AGuIX UNSPs is similar in both types of media, illustrating their colloidal stability. Moreover, an absence of interactions with proteins in serum was noticed, as already reported in others papers [27,38,39]. Soon after dilution, a process of biodegradation occurs as asserted by the USNP size decrease.…”

“…This biodegradation trend is in perfect agreement with relaxometry as well, as shown in SI (figure S5). This method is sensitive to the size of Gd-containing species, and was used in previous biodegradation studies of Gd-based USNP [38,41]. Higher relaxivity values are observed for large objects due to decrease of rotational correlation time, while smaller values are indicative of molecular species.…”

Nanoparticles for MRI-guided radiation therapy: a review

“…The structure of AGuIX involves, as discussed, a polysiloxane core with multiple chelator molecules attached. This structure readily allows the addition of other ligands via "grafting" onto the DOTA molecule, or amine groups on the nanoparticle (Dentamaro et al 2016). This enables additional functionalisation of the AGuIX nanoparticle to support further clinical applications, including additional imaging modalities (including PET and CT), active targeting or its use for applications outside of conventional radiotherapy (Detappe et al 2020;Plissonneau et al 2016;Thakare et al 2019).…”

Imaging Cell Death: Focus on Early Evaluation of Tumor Response to Therapy

“…Meanwhile, this targeted probe also exhibited higher accumulation in irradiated tumors than in untreated tumors . Moreover, a bimodal probe was also developed by grafting E3 to paramagnetic AGuIX nanoparticles previously labeled with a fluorescent dye . Although this bimodal probe could effectively target camptothecin-treated cells, the specificity could not be confirmed because AGuIX nanoparticle grafted with E3 scramble demonstrated a higher targeting efficiency in vitro than nanoparticle grafted with E3 …”