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.

本研究旨在开发一种可生物降解的放射增敏剂，通过增强肿瘤细胞的辐射敏感性并保护正常细胞，以抵消放疗过程中对健康组织的潜在伤害。材料与方法：通过化学沉淀法将铪离子（Hf）引入碳酸钙（CaCO3）纳米粒子中，从而形成Hf:CaCO3纳米粒子。结果与结论：我们的研究结果表明，Hf:CaCO3纳米粒子表现出pH依赖性溶解性，并能够增强放疗在治疗癌细胞方面的疗效。这一研究凸显了Hf:CaCO3纳米粒子作为放疗中双模态放射增敏剂的潜力。放疗是一种常见的癌症治疗方法，利用高能射线破坏癌细胞DNA。然而，它也可能损害健康细胞。为了保护健康细胞并提高治疗效果，我们使用了一种称为放射增敏剂的物质。在我们的研究中，我们利用铪离子（Hf）和CaCO3纳米粒子开发了一种新型放射增敏剂。我们采用化学沉淀法制备这些纳米粒子。我们的测试表明，这些纳米粒子对人体安全，并能提高放疗对癌细胞的疗效，这可能在癌症治疗中成为一种有用的工具。本研究聚焦于通过将铪离子融入碳酸钙纳米粒子（Hf:CaCO3）中，创造一种用于癌症放疗的可生物降解放射增敏剂。放疗作为一种普遍的癌症治疗方法，利用高能电离辐射损伤癌细胞DNA。然而，它也可能对健康组织产生负面影响并引起副作用。放射增敏剂是一种增强肿瘤细胞对辐射敏感性同时最小化辐射剂量的物质。Hf:CaCO3纳米粒子通过化学沉淀法制得，平均粒径约为150 nm，具有CaCO3（方解石）的六方晶体结构，以及由于铪的存在而具有高放射性。乙二醇的分子量显著影响CaCO3粒子形成的大小和形状。在纳米尺度上设计的Hf:CaCO3纳米粒子可以作为载体，通过增强肿瘤部位的渗透和滞留效应，提升药物递送的药理和治疗特性。Hf:CaCO3纳米粒子表现出高生物相容性，并能在类似肿瘤微环境的酸性环境中降解。这种降解有助于平衡肿瘤微环境的pH值，从而抑制肿瘤的生长和扩散。Hf:CaCO3纳米粒子还能增强放疗对癌细胞的疗效，尤其是在铪掺杂水平较高（15 mol%）时。这是因为铪离子在X射线照射下能够产生高能电子，进而产生能够损伤生物分子并导致细胞死亡的活性氧。研究结论表明，作为放疗的双重功能放射增敏剂，Hf:CaCO3纳米粒子可以调节肿瘤微环境的pH值并增强放疗。这使得它们成为癌症治疗中一种有希望的器械。