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.