Interfering biosynthesis by nanoscale metal-organic frameworks for enhanced radiation therapy

Radiation therapy (RT) is one of the most widely used cancer treatments. However, the vigorous biosynthesis of cancer cells plays an important role for RT resistance. Herein, we develop a hafnium-based nanoscale metal-organic frameworks (Hf-nMOFs) loaded with 3-bromopyruvate (3-BrPA) to overcome RT resistance and achieve favorable RT efficacy. The deposition of X-rays is greatly enhanced by Hf-nMOFs to induce stronger damage to DNA in RT. Simultaneously, as an inhibitor of glycolysis, the loaded 3-BrPA can reduce the supply of energy and interfere with the biosynthesis of proteins to decrease the DNA damage repair. As a result, the 3-BrPA@Hf-nMOFs (BHT) will overcome the RT resistance and enhance the curative effect of RT. Up and down-regulated genes as well as the related pathways in cellular metabolism and biosynthesis are well investigated to reveal the radiosensitization mechanism of BHT. In addition, the Hf element endows BHT with CT imaging capability to real-timely monitor the therapeutic process. Hence, the designed strategy of biosynthesis-targeted radiosensitization could decrease the doses of ionizing radiations and provide fresh perspectives on cancer treatment.