Targeted delivery of nano-radiosensitizers for tumor radiotherapy

Radiotherapy is a major tumor treatment approach in clinical, however, the use of high-dose X-rays during therapy inevitably causes damage to nearby healthy tissues, greatly reducing the efficacy and triggering a series of side effects. Advanced nano-radiosensitizers have enhanced tumor sensitivity to X-rays through the physical, chemical, or biological sensitization mechanisms. Nevertheless, they are still hindered by insufficient accumulation in tumors, preventing desired therapeutic effects. With the continuous progress of targeting technology, tumor-targeting delivery systems for nano-radiosensitizers have been developed, which significantly improve the accuracy and efficacy of radiation therapy targeting tumors. In this review article, we summarized the recently emerging strategies for targeting tumors with nano-radiosensitizers and introduced the fundamental principles of physical, chemical, and biological sensitization as well as the potential of targeting technology in radio-sensitization. The mechanisms behind targeted delivery of nano-radiosensitizers to tumors are also discussed from three perspectives: passive targeting, active targeting, and physicochemical targeting. We highlight both challenges and opportunities associated with achieving effective cancer radio-sensitization through targeted approaches, while providing valuable insights for developing novel tumor-targeted radiosensitizer agents and promoting clinical translation. © 2024 Elsevier B.V.