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

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 ²²³RaCl₂ (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.