Self‐Powered α Radionuclide Nanomedicine: Mitochondria‐Targeted Multimodal Energy Recycling for Amplified Radioimmunotherapy

Abstract

Abstract Internal Radionuclide Therapy (IRT) faces significant challenges, particularly the limited controlled penetration depth of conventional β rays and the inefficient targeted delivery of α‐emitters. In this study, a mitochondria‐targeted, self‐powered α radionuclide nanomedicine, and pioneer a groundbreaking “suborganelle precise radiodynamic immunotherapy” paradigm that synergistically integrates physical irradiation, catalytic chemistry, and immunomodulation to overcome the historical limitations of IRT is developed. The innovation establishes a “radionuclide energy internal cycling” strategy through 223 RaCl 2 (the first FDA‐approved α‐emitter), unlocking three synergistic therapies from one radionuclide: precise ionizing radiation, self‐powered catalysis, and immunogenic reprogramming. This paradigm uniquely exploits the full decay spectrum (α particles, β electrons, γ photons) to synchronize physical, chemical, and biological anti‐tumor mechanisms without requiring external energy inputs, offering a transformative solution to overcome the physical‐biological barriers of IRT and bridge localized eradication with systemic immune regulation.