The lecture systematically introduced the core role of radiotherapy in clinical cancer treatment and its inherent shortcomings: on the one hand, the hypoxic tumor microenvironment can easily induce radiotolerance, leading to tumor metastasis, recurrence and treatment failure.； On the other hand, high-dose X-rays can cause serious damage to adjacent normal tissues while killing tumor cells. In response to the above clinical pain points, the speaker proposed the solution of developing new nano-radiotherapy sensitizers, aiming to improve the effect of radiotherapy, reduce radiation dose, alleviate side effects and improve patients' quality of life. In terms of sensitization mechanism, the new strategy of physical sensitization radiotherapy proposed by the research group was highlighted, and a correlation between radiation and copper death was discovered for the first time. Based on this, the team developed a new type of high atomic number (high Z) element nanoradiosensitizer, which can effectively reverse tumor radioresistance by combining with new programmed cell death pathways such as copper death, providing new ideas for the application of multifunctional nanoradiotherapy sensitizers containing copper in immunoradiotherapy. In terms of normal tissue protection, the research team developed a new strategy for the green synthesis of fullerenes, using fullerol nanomaterials as efficient radiation protective agents for the first time, and successfully established a new method of radiation therapy protection covering the skin, gastrointestinal tract, oral mucosa, heart, lungs and other organs. What is particularly noteworthy is that the fullerol radioprotectant has entered the clinical trial stage. Studies conducted on more than 200 radiotherapy patients have shown that it can significantly reduce the incidence of acute radiation dermatitis. The above results are expected to bring safer and more efficient new radiotherapy sensitization and protection solutions to cancer patients, promote the clinical transformation of nanomedicine in the field of radiotherapy, and take a key step towards achieving the treatment goal of "increasing efficiency and reducing toxicity".

This lecture focused on the clinical bottlenecks faced by radionuclide treatment of intermediate and advanced hepatocellular carcinoma, and systematically introduced the construction and application of a new type of nuclide-sensitized nanosystem. The speaker pointed out that although radionuclide therapy has shown significant advantages in intermediate and advanced liver cancer, the poor permeability of tumor tissue and radioresistance caused by the complex DNA damage repair mechanism of tumor cells make it difficult for internal radiotherapy alone to effectively suppress metastatic tumors. In response to the above problems, the research team proposed a potential strategy, which is to combine the therapeutic radionuclide 177Lu with the ultraminiaturized radiosensitizer HfO2 loaded with ataxia telangiectasia mutation and RAD 3-related kinase inhibitor (ATRi) to construct a radionuclide-sensitized nanosystem. This system can improve the internalization and penetration efficiency of nanomedicines by tumor cells, thereby enhancing the local radiation effect and reducing the risk of lung metastasis. The lecture focused on the research on the therapeutic efficacy and mechanism of this nanosystem in rabbit orthotopic liver cancer and spontaneous lung metastasis models. The results showed that this strategy can significantly inhibit the growth of orthotopic tumors and the formation of lung metastases, providing new ideas and experimental basis for overcoming radioresistance of liver cancer and improving the efficacy of radionuclide therapy.