Nanopartículas y radioterapia: evaluación del potencial de una nanoplataforma dopada con iones lantánidos como un agente radiosensibilizador en el tratamiento de glioblastoma en un modelo in vitro
Thesis
Glioblastoma is a tumour located in the central nervous system and is considered one of the most aggressive tumours, which is why it is classified by the World Health Organisation (WHO) as grade IV [1], [2]. This type of tumour has multiple mechanisms to evade treatment and manages to rapidly and progressively invade nerve tissue. Currently, its treatment is based on a combination of surgery, radiotherapy and, in some specific cases, chemotherapy [2]. In the case of radiotherapy, there are two major challenges: the first is to eradicate tumour tissue while ensuring minimal damage to surrounding healthy tissue; the second challenge lies in the phenomenon of tumour radioresistance, i.e. the ability of the tumour to resist the destructive effects of ionising radiation. For this reason, the incorporation of radiosensitising agents has been explored to increase the dose received by the tumour and avoid damage to adjacent tissue [3]. In recent years, some types of nanoparticles have played an important role in this type of application due to their particular characteristics such as their size, composition and biocompatibility, which make them capable of interacting with ionising radiation, increasing the deposited dose and thus potentially increasing the efficiency of this type of therapy [4]. In the specific case of the use of nanoparticles as radiosensitising agents in radiotherapy, it is sought that these contain in their composition elements or chemical species with a high number of electrons, which can generate secondary emissions in the irradiation process and therefore the dose applied to tumours is higher. Carbon dots (CPs) are a new type of carbon-based nanoparticles, attractive for their biocompatibility, biodistribution, optical properties and ease of synthesis. Additionally, this type of nanoparticles has the ability to add atoms with high atomic number in their composition [5]. In this work, lanthanide ion doped carbon dots based nanoplatforms were developed for preliminary evaluation as radiosensitising agent in the treatment of glioblastoma. PCs are synthesised by microwave method at a temperature of 200°C using urea and citric acid as organic precursors. In the synthetic process, diethylenetriaminepentaacetic acid gadolinium(iii) salt dihydrogen hydrate and ytterbium(III) chloride hexahydrate are included as the lanthanide ion precursors in order to increase the electronic cloud that will interact with the ionising energy beams. The synthesised nanoplatforms (PC: PC:Gd3+ and PC:Gd3+,Yb3+) were characterised by atomic force microscopy (AFM), Z-potential, fluorescence, UV-Vis and infrared spectroscopy. The cytotoxic effect was then evaluated in different cancer and non-cancer cell lines and primary cultures as a function of the concentrations of the nanoplatforms, observing that PC, PC:Gd3+ and PC:Gd3+,Yb3+ are not cytotoxic at concentrations below 500µg/mL and that in non-cancer cells cell viability is lower than in cancer cells exposed to the treatments. In order to gain initial insights into the radiosensitising potential of these nanoplatforms, cell lines and primary cultures were incubated with these treatments and subsequently irradiated. This process was carried out at the Cancer Control Centre on the basis of a previous irradiation protocol. After seeding the irradiated cells, their cell proliferation capacity was analysed, obtaining the survival fraction curve for the U87 cell line and the primary glioma cultures, showing a decrease in the survival fraction of the cells with treatment (PC and PC:Gd3+) with respect to the cells without treatment. Thus concluding a possible potential as a radiosensitising agent in the treatment of glioblastoma, by means of the in vitro assay.
