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Article dans une revue Theranostics Année : 2023

Tuning ultrasmall theranostic nanoparticles for MRI contrast and radiation dose amplification

Ross Berbeco
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Résumé

Background: The introduction of magnetic resonance (MR)-guided radiation treatment planning has opened a new space for theranostic nanoparticles to reduce acute toxicity while improving local control. In this work, second-generation AGuIX ® nanoparticles (AGuIX-Bi) are synthesized and validated. AGuIX-Bi are shown to maintain MR positive contrast while further amplifying the radiation dose by the replacement of some Gd 3+ cations with higher Z Bi 3+. These next-generation nanoparticles are based on the AGuIX ® platform, which is currently being evaluated in multiple Phase II clinical trials in combination with radiotherapy. Methods: In this clinically scalable methodology, AGuIX ® is used as an initial chelation platform to exchange Gd 3+ for Bi 3+. AGuIX-Bi nanoparticles are synthesized with three ratios of Gd/Bi, each maintaining MR contrast while further amplifying radiation dose relative to Bi 3+. Safety, efficacy, and theranostic potential of the nanoparticles were evaluated in vitro and in vivo in a human non-small cell lung cancer model. Results: We demonstrated that increasing Bi 3+ in the nanoparticles is associated with more DNA damage and improves in vivo efficacy with a statistically significant delay in tumor growth and 33% complete regression for the largest Bi/Gd ratio tested. The addition of Bi 3+ by our synthetic method leads to nanoparticles that present slightly altered pharmacokinetics and lengthening of the period of high tumor accumulation with no observed evidence of toxicity. Conclusions: We confirmed the safety and enhanced efficacy of AGuIX-Bi with radiation therapy at the selected ratio of 30Gd/70Bi. These results provide crucial evidence towards patient translation.
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Dates et versions

hal-04222633, version 1 (02-10-2023)

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Needa Brown, Paul Rocchi, Léna Carmès, Romy Guthier, Meghna Iyer, et al.. Tuning ultrasmall theranostic nanoparticles for MRI contrast and radiation dose amplification. Theranostics, 2023, 13, pp.4711 - 4729. ⟨10.7150/thno.85663⟩. ⟨hal-04222633⟩
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