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Alumino- and bioactive-silicate glasses as effective yttrium carriers for in situ radiotherapeutic applications

铝硅酸盐玻璃和生物活性硅酸盐玻璃作为原位放射治疗应用的有效钇载体

基本信息

批准号：
EP/F020066/1
负责人：
Antonio Tilocca
金额：
$ 33.84万
依托单位：
University College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FF020066%2F1
关键词：
Alumino bioactive silicate glasses effective

项目摘要

Radiotherapy for the treatment of cancer is generally performed irradiating the tumour from an external source: the need to avoid unnecessary exposure to radiation and consequent damage to healthy surrounding tissues can result in ineffective treatment when irradiating some deep seated tumours, such as liver or kidney. In-situ radiotherapy, on the other hand, is performed by directly injecting the radionuclides in the blood vessels supplying the tumour, thus delivering a high, localized dose of radiation, where the surrounding tissues are not significantly affected. In order for this task to be performed effectively, a suitable carrier is needed to transport the radionuclide to the tumour target site and lock it there; the carrier should have long enough durability in the physiological environment, so that it will not dissolve, releasing the active ions, before their radiation decay. At the same time, the carrier should have high biocompatibility, do not release any harmful element in the physiological environment, and should possess physical and mechanical properties suitable to be suspended and transported in the blood stream, up to the target site.In this project, we will focus on yttrium-containing alumino-silicate (YAS) and bioactive (YB) glasses, and investigate their structure, dynamics and surface reactivity, in order to probe and understand their potential as carriers for radiotherapeutic applications. Aluminosilicate glass microspheres containing radioactive yttrium are currently employed with success to treat liver cancer; another exciting possibility is to employ bioactive glasses as yttrium carriers. The latter have the potential to improve the long-term biodegradability of the microspheres, while keeping the very slow yttrium release rate necessary for radiotherapy applications. Computer simulations will be used to provide an accurate microscopic picture of these materials, with particular focus on the features concerning the yttrium ions: their local coordination, the way they are incorporated in the glass network and their mobility are key properties which affect the ability of the glass carrier to lock them at the tumour site for a time long enough to deliver their radiation dose. We will model and compare different glass compositions, in order to highlight the effect of compositional changes on the above properties, and on other physical properties of the glasses relevant for these applications: this information will directly support the optimization of bioactive glasses for radiotherapy.Since radiotherapy, as many other medical applications of glasses, involve glass particles in direct contact with a physiological environment, the final aim of the project is to extend the (bulk) studies described above to model the active glass/water interface. We will use Molecular Dynamics techniques to build a reliable model of the hydrated glass surface, providing a detailed dynamical picture of the processes occurring on the surface upon hydration, which have a central role in the partial dissolution of the glass network. The outcome of this research will be a rather complete description of structural, dynamical and surface effects relevant to the applications of YAS and YB glasses as carriers of radionuclide ions.The investigations will focus on yttrium but many general aspects should be common to the incorporation of other radionuclides, such as rhenium. The simulations will ultimately indicate whether and how the glass composition can be fine-tuned to improve the properties of the glass crucial for its radiotherapeutic use, such as solubility. Understanding key composition-structure-properties relationships of these materials at an atomistic level will be an important step towards a more rational design of biomaterials for these applications, and will answer recent calls within the biomaterials community for more fundamental approaches to technological developments in this field.

用于治疗癌症的放射治疗通常是从外部源照射肿瘤：在照射一些深部肿瘤（例如肝脏或肾脏）时，需要避免不必要的辐射暴露以及对健康周围组织的损害，可能会导致治疗无效。另一方面，原位放射治疗是通过直接将放射性核素注射到供应肿瘤的血管中来进行的，从而提供高剂量的局部放射线，而周围组织不会受到明显影响。为了有效地完成这项任务，需要合适的载体将放射性核素运输到肿瘤靶位并将其锁定在那里；载体在生理环境中应具有足够长的耐久性，以便在辐射衰减之前不会溶解并释放活性离子。同时，载体应具有较高的生物相容性，在生理环境中不释放任何有害元素，并应具有适合在血流中悬浮和运输直至目标部位的物理和机械性能。在本项目中，我们将重点关注含钇铝硅酸盐（YAS）和生物活性（YB）玻璃，研究它们的结构、动力学和表面反应性，以探究和了解它们作为放射治疗应用的载体。含有放射性钇的铝硅酸盐玻璃微球目前已成功用于治疗肝癌；另一个令人兴奋的可能性是使用生物活性玻璃作为钇载体。后者有可能提高微球的长期生物降解性，同时保持放射治疗应用所需的非常缓慢的钇释放速率。计算机模拟将用于提供这些材料的精确显微图像，特别关注与钇离子有关的特征：它们的局部配位、它们融入玻璃网络的方式以及它们的迁移性是影响玻璃载体将它们锁定在肿瘤部位足够长的时间以传递辐射剂量的能力的关键特性。我们将对不同的玻璃成分进行建模和比较，以突出成分变化对上述性能以及与这些应用相关的玻璃的其他物理性能的影响：该信息将直接支持用于放射治疗的生物活性玻璃的优化。由于放射治疗与玻璃的许多其他医学应用一样，涉及与生理环境直接接触的玻璃颗粒，该项目的最终目标是将上述（批量）研究扩展到对活性玻璃/水界面进行建模。我们将使用分子动力学技术建立水合玻璃表面的可靠模型，提供水合时表面发生的过程的详细动态图，这些过程在玻璃网络的部分溶解中起着核心作用。这项研究的结果将是对与 YAS 和 YB 玻璃作为放射性核素离子载体的应用相关的结构、动力学和表面效应的相当完整的描述。研究将集中于钇，但许多一般方面对于掺入其他放射性核素（例如铼）应该是相同的。模拟最终将表明是否以及如何微调玻璃成分，以改善对其放射治疗用途至关重要的玻璃性能，例如溶解度。在原子水平上理解这些材料的关键组成-结构-性能关系将是朝着更合理地设计这些应用的生物材料迈出的重要一步，并将响应生物材料界最近对该领域技术发展的更基本方法的呼吁。