Self‐Powered α Radionuclide Nanomedicine: Mitochondria‐Targeted Multimodal Energy Recycling for Amplified Radioimmunotherapy
Xian Li, Chao-Chao Wang, Yelin Wu, Jiajia Zhang, Han Zhang, Shanshan Qin, Linglin Tang, Fei Yu
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.