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Evaluation of the active targeting of melanin granules after intravenous injection of dendronized nanoparticles

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Bordeianu, Catalina | Parat, Audrey | Piant, Sébastien | Walter, Aurélie | Zbaraszczuk-Affolter, Christine | Meyer, Florent | Bégin-Colin, Sylvie | Boutry, Sébastien | Jouberton, Elodie | Chezal, Jean-Michel | Labeille, Bruno | Cinotti, Elisa | Perrot, Jean-Luc | Miot-Noirault, Elisabeth | Laurent, Sophie | Felder-Flesch, Delphine | Muller, Robert N.

Edité par CCSD ; American Chemical Society -

International audience. The biodistribution of dendronized iron oxides, NPs10@D1_DOTAGA and melanin-targeting NPs10@D1_ICF_DOTAGA, was studied in vivo using MRI and planar scintigraphy through [177Lu]Lu-radiolabeling. MRI experiments showed high contrast power of both dendronized nanoparticles (DPs) and hepatobiliary and urinary excretions. Little tumor uptake could be highlighted after intravenous injection probably as a consequence of the negatively charged DOTAGA-derivatized shell which reduces the diffusion across the cells' membrane. Planar scintigraphy images demonstrated a moderate specific tumor uptake of melanoma-targeted [177Lu]Lu-NPs10@D1_ICF_DOTAGA at 2 h post intravenous injection, and the highest tumor uptake of the control probe [177Lu]Lu-NPs10@D1_DOTAGA at 30min pi, probably due to the enhanced permeability and retention (EPR) effect. In addition, ex vivo Confocal microscopy (EVCM) studies showed a high specific targeting of human melanoma samples impregnated with NPs10@D1_ICF_Alexa647_ DOTAGA.

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