Abstract
In 2022, there were approximately 18.74 million new cancer cases and about 9.67 million cancer deaths globally. On the one hand, the high incidence, high metastatic potential, and high mortality rate of cancer make it one of the major threats to human life and health. On the other hand, the inefficiency of traditional cancer treatment methods such as surgical resection, radiotherapy, and chemotherapy, as well as their irreversible side effects on normal tissues, result in an extremely low cure rate for advanced cancer. Therefore, early diagnosis and treatment of cancer are of great significance in improving the cure rate for cancer patients. In recent years, with the continuous progress of nanotechnology, emerging non-invasive cancer treatment methods such as photothermal therapy (PTT), photodynamic therapy (PDT), and sonodynamic therapy (SDT) have shown advantages of high efficiency, ease of operation, and minimal side effects, gradually becoming a trend in cancer treatment research. Bismuth-based nanomaterials, due to the inherent CT imaging advantages of bismuth and its excellent safety and stability, have demonstrated great potential in cancer diagnosis and treatment. Therefore, this thesis aims to explore and develop bismuth-based nanomaterials with high-performance cancer diagnostic and therapeutic effects, optimize their preparation methods, and achieve controllable synthesis.In chapter 3, the preparation methods, morphological characterization, and optimization processes of oxygen-defect BiOCl nanosheet were systematically studied. The influence of reducing agents in the defect treatment on the morphology of nanomaterials was also discussed. By controlling the parameters of the synthesis reaction, such as time, temperature, and surfactants, the morphology of the products was optimized, ultimately achieving controllable preparation of bismuth-based nanomaterials.
In chapter 4, oxygen-defect bismuth oxychloride (BiOCl) nanosheets were designed to realize the sonodynamic and second near-infrared photo-induced (NIR-II) therapy of breast cancer. It was found that ultrasonic irradiation significantly improved the heat conversion of oxygen-defect BiOCl nanosheets. Upon ultrasonic irradiation, the local high temperature and high pressure generated by the ultrasonic cavitation effect combined with the thermoelectric and piezoelectric effects of oxygen-defect BiOCl nanosheets create a built-in electric field. This facilitates the separation of carriers, increasing their mobility and extending their lifetimes, thereby greatly improving the effectiveness of SDT and NIR-II phototherapy. In addition, this treatment strategy also improves the therapeutic effect of traditional sonodynamic therapy on hypoxic cancer cells. This is because photothermal therapy does not require the participation of oxygen, and sonodynamic therapy and NIR-II phototherapy have a synergistic enhanced treatment mechanism in oxygen-defect BiOCl nanosheets.
Since the ultrasonic cavitation effect at the microscopic level is the nucleation, growth and implosion of microbubbles in a very short time, such a process is difficult to study experimentally. Therefore, in this chapter, density functional theory (DFT) calculations and COMSOL simulations were used to study the performance regulation of oxygen defect BiOCl nanosheets by the ultrasonic cavitation effect at the macroscopic level. It was found that the introduction of oxygen vacancies in BiOCl nanosheets forms an intermediate state between the conduction band and the valence band in the energy band structure of the material, reducing the band gap, extending the lifetime and utilization rate of carriers, thereby enhancing photo-induced and sonodynamic effects. Additionally, in COMSOL simulations, when the temperature and pressure changes caused by ultrasonic cavitation effects are applied to oxygen-defect BiOCl nanosheets, a distinct trend in the potential distribution on the surface of the oxygen-defect BiOCl nanosheets was observed. This potential difference forms an electric field that promotes the separation of charge carriers and extends their lifetime, explaining the synergistic enhancement effect of sonodynamic therapy and NIR-II phototherapy strategies. Therefore, this treatment strategy demonstrates ~88.6 % and ~91 % elimination rate against deep-seated tumor cells under hypoxic conditions and normoxic conditions, respectively. Furthermore, due to the high X-ray attenuation of Bi and excellent NIR-II absorption, oxygen-defect BiOCl nanosheets enable precise cancer diagnosis through photoacoustic (PA) imaging and computed tomography (CT).
In chapter 5, this chapter continues the study of bismuth oxyhalide nanomaterials, designing and preparing oxygen-defect bismuth oxyiodide (BiOI) quantum dots for Dual-CT and PA imaging-guided cancer SDT. Iodine, due to its excellent X-ray attenuation ability, has been widely used in commercial CT contrast agents. Thus, the presence of two CT imaging elements (Bi and I) in BiOI quantum dots simultaneously endows them with excellent CT contrast capabilities. Compared to the oxygen-defect BiOCl nanosheets studied in Chapter 4, the oxygen-defect BiOI quantum dots exhibit dual-energy CT capabilities due to the different sensitivities of iodine and bismuth elements to X-rays of different energies.
The introduction of oxygen vacancies reduces the bandgap of the BiOI quantum dots, allowing the material to be excited by ultrasound to generate charge carriers for SDT. Reduced bandgap endows the oxygen-defect BiOI quantum dots with excellent optical absorption properties, which can be used for PA imaging. Unlike two-dimensional nanosheets, zero-dimensional quantum dots have an extremely small size (< 5 nm), enabling the oxygen-defect BiOI quantum dots to escape more liver capture and effectively accumulate at the tumor site. Therefore, under the same ultrasound irradiation power and treatment time, oxygen-defect BiOI quantum dots exhibit better SDT effects compared to oxygen-defect BiOCl nanosheets.
In conclusion, this PhD work developed and studied two novel bismuth-based nanomaterials with excellent cancer diagnosis and treatment performances, aiming to address existing issues in non-invasive cancer treatment technologies and provide new ideas for early cancer diagnosis and treatment. The preparation process of those nanomaterials, morphological characterization, and the validation of effects at cellular and animal levels have all been systematically studied. The designed oxygen-defect BiOCl nanosheets expanded the biomedical application of bismuth oxyhalide nanomaterials to the 1208 nm second near-infrared window range. The phenomenon of ultrasound cavitation effect enhancing the tumor treatment efficacy of oxygen-defect BiOCl was discovered and explained. The issue of poor treatment effect of traditional SDT on hypoxic tumor areas has improved. Furthermore, Bismuth oxyhalide nanomaterials with dual-energy CT imaging capabilities were developed.
| Date of Award | 15 Oct 2025 |
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| Original language | English |
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| Supervisor | Xiaogang Yang (Supervisor), Aiguo Wu (Supervisor) & Guang Li (Supervisor) |