Radiotherapy Mediated Catalytic Prodrug Therapy with Higher Radiochemical Conversion than Hydrated Electrons

Using radiotherapy to activate chemotherapeutic conversion is a promising approach to reduce off-target toxicity in cancer therapy. Current radiation chemistry mostly relies on substrate to react with the primary species of water radiolysis, with the most abundant being hydrated electron (e−aq) and ·OH. However, only 280 nM e−aq is generated by 1 Gy radiation, fundamentally limiting the yield of conventional radiation chemistry. Here, we show a radiation-mediated catalyst significantly boosts the radiochemical conversion of caged compounds. Palladium precatalyst could be transformed to active Pd(0) by γ-ray of as low as 1 Gy. The radiochemical yield can reach 2750 nM/Gy, which is 10 times that of e−aq. The strategy works even when obstructed by 15 cm of animal tissue. We demonstrate its functionality within live cells, showcasing the synergistic radiation-directed chemotherapy. We anticipate the altered mechanism of action to be a starting point for using bio-compatible dose of ionizing radiation to chemically manipulate deep tissue.