Biodegradable hafnium-doped CaCO₃ nanoparticles as a dual-modality radiosensitizer for cancer radiotherapy

Aim: Radiotherapy employs high-energy ionizing radiation to inflict DNA damage on cancer cells, thereby causing their demise. However, this procedure can inadvertently harm healthy tissue. Thus, this study aimed to develop biodegradable radiosensitizers that counteract these adverse effects by enhancing the radiation sensitivity of tumor cells and safeguarding normal cells. Materials & methods: A biodegradable radiosensitizer was engineered by incorporating hafnium ions (Hf) into calcium carbonate (CaCO3) nanoparticles via a chemical precipitation technique, resulting in the formation of Hf:CaCO3 nanoparticles. Results & conclusion: Our findings demonstrate that Hf:CaCO3 nanoparticles exhibit pH-dependent solubility and can augment the efficacy of radiotherapy in treating cancer cells. This research underscores the potential of Hf:CaCO3 nanoparticles as a dual-modality radiosensitizer in radiotherapy. Radiotherapy is a common cancer treatment that uses high-energy rays to kill cancer cells. However, it can also harm healthy cells. To protect healthy cells and make the treatment more effective, we use something called radiosensitizers. In our study, we made a new kind of radiosensitizer using hafnium ions (Hf) and CaCO3 nanoparticles. We made these nanoparticles using a method called chemical precipitation. Our tests showed that these nanoparticles are safe for the body and can make radiotherapy more effective against cancer cells, which could be a useful tool in cancer treatment. The research focuses on creating a biodegradable radiosensitizer for cancer radiotherapy by incorporating hafnium ions into calcium carbonate nanoparticles (Hf:CaCO3). Radiotherapy, a prevalent cancer treatment, uses high-energy ionizing radiation to damage cancer cell DNA. However, it can also negatively affect healthy tissue and cause side effects. Radiosensitizers are substances that enhance tumor cell sensitivity to radiation while minimizing the radiation dose. Hf:CaCO3 nanoparticles are produced using a chemical precipitation technique. These nanoparticles have an average size of approximately 150 nm, a hexagonal crystal structure of CaCO3 (vaterite), and high radiopacity due to the presence of Hf. The molecular weight of ethylene glycol significantly influences the size and shape of CaCO3 particle formation. Hf:CaCO3 nanoparticles, when engineered at the nanoscale, can serve as a vehicle to enhance the pharmacological and therapeutic properties of drug delivery through the enhanced permeation and retention effect at tumor sites. Hf:CaCO3 nanoparticles exhibit high biocompatibility and can degrade in acidic environments like the tumor microenvironment. This degradation can help balance the pH of the tumor microenvironment, thereby inhibiting tumor growth and spread. Hf:CaCO3 nanoparticles can also boost the efficacy of radiotherapy on cancer cells, particularly when the Hf doping level is high (15 mol %). This is because Hf ions can generate high-energy electrons under x-ray irradiation, leading to the production of reactive oxygen species that can damage biological molecules and cause cell death. The research concludes that Hf:CaCO3 nanoparticles, as dual-functional radiosensitizers for radiotherapy, can regulate the pH value of the tumor microenvironment and enhance radiotherapy. This makes them a promising instrument in cancer treatment.研究目的：放疗（Radiotherapy）借助高能电离辐射诱导癌细胞DNA损伤，从而实现癌细胞的杀灭，但该治疗过程可能会意外损伤正常组织。为此，本研究旨在开发可生物降解的放射增敏剂（radiosensitizer），通过增强肿瘤细胞的辐射敏感性同时保护正常细胞，以抵消放疗带来的上述不良反应。 材料与方法：本研究采用化学沉淀法，将铪离子（hafnium ions, Hf）掺入碳酸钙（calcium carbonate, CaCO₃）纳米颗粒（nanoparticle）中，成功制备得到Hf:CaCO₃纳米颗粒，即目标可生物降解放射增敏剂。 结果与结论：本研究结果表明，Hf:CaCO₃纳米颗粒具备pH依赖溶解性，可显著增强放疗对癌细胞的治疗效果。本研究证实了Hf:CaCO₃纳米颗粒作为双模态放射增敏剂在放疗领域的应用潜力。 放疗是临床常见的癌症治疗手段，通过高能射线杀灭癌细胞，但同时也会对正常细胞造成损伤。为保护正常细胞并提升治疗效果，临床常使用放射增敏剂。本研究制备了一种新型放射增敏剂，通过化学沉淀法合成了铪离子掺杂碳酸钙纳米颗粒（Hf:CaCO₃）。实验结果显示，该纳米颗粒具有良好的生物安全性，可有效增强放疗对癌细胞的杀伤效果，有望成为癌症治疗的实用工具。 本研究聚焦于开发用于癌症放疗的可生物降解放射增敏剂，通过将铪离子掺入碳酸钙纳米颗粒中制备得到Hf:CaCO₃纳米颗粒。 放疗作为一种主流癌症治疗手段，利用高能电离辐射损伤癌细胞DNA，但同时也会对正常组织造成负面影响并引发不良反应。放射增敏剂是一类能够增强肿瘤细胞对辐射的敏感性，同时降低辐射剂量的物质。 本研究通过化学沉淀法制备得到Hf:CaCO₃纳米颗粒，该颗粒平均粒径约150 nm，具有碳酸钙的六方晶型——球霰石（vaterite），且因铪离子的存在而具备高放射不透性。 乙二醇的分子量对碳酸钙颗粒的成核尺寸与形貌具有显著影响。 纳米尺度的Hf:CaCO₃纳米颗粒可作为递送载体，通过肿瘤部位的增强渗透滞留效应（enhanced permeation and retention effect, EPR效应）提升药物递送的药理学与治疗学性能。 Hf:CaCO₃纳米颗粒具有优异的生物相容性，可在肿瘤微环境等酸性环境中发生降解，该降解过程可调节肿瘤微环境的pH值，进而抑制肿瘤的生长与转移。 当铪离子掺杂量较高（15 mol%）时，Hf:CaCO₃纳米颗粒可显著提升放疗对癌细胞的杀伤效果，其机制在于铪离子在X射线（X-ray）照射下可产生高能电子，进而诱导活性氧（reactive oxygen species）的生成，损伤生物大分子并引发细胞死亡。 本研究最终证实，Hf:CaCO₃纳米颗粒作为放疗用双功能放射增敏剂，可调节肿瘤微环境的pH值并增强放疗效果，是一种极具应用前景的癌症治疗工具。