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Communication Dans Un Congrès Année : 2019

Transfer of the ultrasmall theranostic gadolinium-based nanoparticle AGuIX® to clinical medicine

C. Rodriguez-Lafrasse
G. Ollier
  • Fonction : Auteur
Delphine Vernos
  • Fonction : Auteur
Lucie Sancey

Résumé

AGuIX® (Activation-and-Guidance by Irradiation X) are sub-5nm theranostic nanoparticles composed of a polysiloxane matrix and gadolinium chelates. Developed by the Lyon University, they underwent extensive pre-clinical evaluation and were recently translated to clinical evaluation in the treatment of brain metastases and advanced cervical cancer. This presentation will summarize the principal in cellulo and pre-clinical results that led to their first-in-man administration.In collaboration with other teams, we did the proof of concept of their radiosensitizing efficacy in cellular (2D/3D cultures) and preclinical models of three radioresistant tumors: head and neck squamous cell carcinoma, metastatic melanoma and chondrosarcoma tumors (Miladi et al, Nanomedicine 2015; Kotb et al, Theranostics 2016; Ollier et al, in preparation). AGuIX® enter cancer cells by passive diffusion and macropinocytosis, localize in cytoplasm as free particle or entrapped in lysosomes, in close vicinity to the mitochondria (Rima et al, Biomaterials 2013). The interaction of radiation with gadolinium atoms produce a variety of secondary emissions, such as Auger shower, leading to the production of high reactive oxygen species levels that can trigger an intra‐mitochondrial stress and nuclear DNA damage leading to cell death (Simonet al., submitted). Relative biological efficiency (RBE) in cancer cells is quite comparable to that observed in response to carbon ions, suggesting the existence of common mechanisms through the amplification of the local dose (Wozny et al, Nanomedicine 2017). AGuIX®nanoparticles have already shown their efficiency as a radiosensitizer in at least 12 preclinical models of cancer (Lux et al, BJR 2018). Biodistribution studies after intravenous administration have shown passive uptake of the nanoparticles in tumors due to enhanced permeability and retention (EPR) effect combined with rapid renal elimination. We are now testing the next generation of AGuIX® nanoparticles containing other metals or functionalized with therapeutic or targeting moieties (D. Vernos’ poster).Supported by LabEx PRIMES

Domaines

Cancer
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Dates et versions

hal-02355627 , version 1 (08-11-2019)

Identifiants

  • HAL Id : hal-02355627 , version 1

Citer

C. Rodriguez-Lafrasse, M.-T. Aloy, G. Ollier, Delphine Vernos, Riad Ladjohounlou, et al.. Transfer of the ultrasmall theranostic gadolinium-based nanoparticle AGuIX® to clinical medicine. ICRR 2019, Aug 2019, Manchester, United Kingdom. ⟨hal-02355627⟩
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