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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.
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