Fluorinated nanohybrid micelles carrying 177Lu, gold, and oxygen for potentiated internal radiotherapy.

We report the development of a micellar nanocarrier designed for internal radiotherapy applications. Fluorinated amphiphiles were self-assembled into stable micelles and engineered as multifunctional nanoplatforms by incorporating gold nanoparticles, molecular oxygen, and the therapeutic radionuclide lutetium-177. This integrated design combines radiotherapeutic emission from 177Lu, radiosensitization through gold-mediated dose enhancement, and local oxygen delivery to mitigate tumor hypoxia and improve radiation response. The resulting nanohybrid micelles were evaluated both in vitro and in vivo as radiation nanomedicines. With B16F10 melanoma cells, AuNP@[177Lu]Lu-micelles exhibited significantly enhanced radiocytotoxicity compared to [177Lu]Lu-micelles without gold, highlighting the synergistic effect of nanoparticle-mediated radiosensitization. In vivo, a single intratumoral injection in mice bearing subcutaneous B16F10 tumors enabled sustained tumor growth control. Notably, despite the intrinsic radioresistance of the B16F10 model, AuNP@[177Lu]Lu-micelles achieved approximately 78% inhibition of tumor growth at day 7 post-treatment, underscoring the therapeutic potential of this multifunctional system.