Hafnium-Based MOF-Derived Porous Carbon Nanoplatform For Breast Cancer Radiotherapy Research

Breast cancer is one of the most commonly diagnosed cancers in women worldwide,and is a leading cause of cancer-related deaths in women globally,posing a serious threat to the physical and mental health of women.Breast cancer is a heterogeneous disease,with significant individual differences in tumor growth rate,invasiveness,clinical response,drug sensitivity,prognosis,and other aspects.Common clinical treatment methods for breast cancer include surgical treatment,radiation therapy,chemotherapy,endocrine therapy,and targeted therapy,each with its own advantages and disadvantages.Among them,radiation therapy is an important treatment for breast cancer,which can be used for some patients who cannot undergo surgery,and for treating local metastatic lesions.Especially after breast-conserving surgery,radiation therapy can reduce the possibility of local recurrence.However,the inherent limitations of radiation therapy and the radiation resistance of tumor tissues are the main problems in current breast cancer treatment,and it is urgently needed to reduce the radioresistance of cancer cells and improve the radiation sensitivity of tumor tissues to enhance the effectiveness of radiotherapy.In recent years,the development and application of nano-radiosensitizers have provided new methods and ideas to overcome the problems faced by current radiotherapy.Nano-radiosensitizers containing high atomic number（high-Z）elements are often used to enhance cancer radiotherapy because they can promote radiation energy deposition and the generation of reactive oxygen species（ROS）.Porous carbon materials derived from metal-organic framework（MOF）are a new type of porous carbon nanomaterial obtained by the high-temperature pyrolysis of MOF as precursors.Compared with traditional carbon materials,they retain the rich pore structure,controllable morphology,and uniform distribution of single atoms or metal nanoparticles of MOF materials,and have broad application prospects in the biomedical field.Therefore,high-Z MOF-derived porous carbon materials can be used as a new type of radiosensitizer,but there is currently a lack of related research reports.In this thesis,using porous carbon material derived from hafnium-based MOF as a nano platform,functional nano radiotherapy sensitizer was designed and synthesized to overcome radiotherapy resistance of breast cancer cells and enhance radiotherapy efficacy.1.A high-density,ultra-small hafnium oxide（HfO₂）embedded porous carbon nano-material（HPCN）was prepared using hafnium-based MOF as precursors as a multifunctional nano-radiosensitizer to overcome radioresistance of breast cancer cells and enhance the effectiveness of radiation therapy.The porous carbon framework of HPCN gives it good peroxidase-like activity and near-infrared second window（NIR-II）absorption and photothermal conversion properties.This effect can catalyze H₂O₂ in the tumor into·OH,induce tumor cell oxidative stress,and also can be used for tumor photothermal therapy,enhancing vascular permeability and improving tumor oxygenation,further increasing the sensitivity of tumor cells to radiation therapy.Finally,under X-ray irradiation,the uniformly dispersed ultra-small Hf O₂ in HPCN produces a large number of high-energy electrons to kill cancer cells through doseancement effects.Ultimately,the nano-radiosensitizer can effectively improve the effectiveness of radiation therapy through multiple mechanisms.2.A hafnium-based MOF-derived nanoprobe was designed for hypoxia-guided radiosensitization therapy of breast cancer.Hf-MOF was carbonized to obtain a porous carbonized nanomaterial containing ultra-small hafnium oxide（Hf C）,and then a fluorescent-labeled hypoxia-inducible factor（HIF-α）antisense nucleotide chain was adsorbed onto Hf C to construct a nanosensor（Hf C-Hy）whose fluorescence was quenched by Hf C.The HIF-αantisense nucleotide chain in Hf C-Hy can hybridize with HIF-αm RNA and restore its fluorescence signal,thus used to evaluate the degree of tumor hypoxia to guide radiotherapy.The Hf C nanomaterial containing Hf O₂ can deposit more radiation energy in cancer cells to enhance radiosensitivity.Therefore,this sensor helps to develop treatment plans by timely evaluating the degree of hypoxia,providing an alternative strategy for improving clinical tumor treatment.