Selenium‐Doped Nanoheterojunctions for Highly Efficient Cancer Radiosensitization

Abstract Exploring efficient and low‐toxicity radiosensitizers to break through the bottleneck of radiation tolerance, immunosuppression and poor prognosis remains one of the critical developmental challenges in radiotherapy. Nanoheterojunctions, due to their unique physicochemical properties, have demonstrated excellent radiosensitization effects in radiation energy deposition and in lifting tumor radiotherapy inhibition. Herein, they doped selenium (Se) into prussian blue (PB) to construct a nano‐heterojunction (Se@PB), which could promote the increase of Fe²⁺/Fe³⁺ ratio and conversion of Se to a high valence state with Se introduction. The Fe²⁺‐Se‐Fe³⁺ electron transfer chain accelerates the rate of electron transfer on the surface of the nanoparticles, which in turn endows it with efficient X‐ray energy transfer and electron transport capability, and enhances radiotherapy physical sensitivity. Furthermore, Se@PB induces glutathione (GSH) depletion and Fe²⁺ accumulation through pro‐Fenton reaction, thereby disturbs the redox balance in tumor cells and enhances biochemical sensitivity of radiotherapy. As an excellent radiosensitizer, Se@PB effectively enhances X‐ray induced mitochondrial dysfunction and DNA damage, thereby promotes cell apoptosis and synergistic cervical cancer radiotherapy. This study elucidates the radiosensitization mechanism of Se‐doped nanoheterojunction from the perspective of the electron transfer chain and biochemistry reaction, which provides an efficient and low‐toxic strategy in radiotherapy.