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Acceso Abierto
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
| dc.contributor.advisor | Rodríguez Burbano, Diana Consuelo | |
| dc.creator | Ochoa Paipilla, Mayerly Natalia | |
| dc.creator.degree | Magíster en Ingeniería Biomédica | |
| dc.creator.degreeLevel | Maestría | |
| dc.date.accessioned | 2024-07-17T00:57:25Z | |
| dc.date.available | 2024-07-17T00:57:25Z | |
| dc.date.created | 2024-06-21 | |
| dc.description | El glioblastoma es un tumor situado en el sistema nervioso central y es considerado como uno de los tumores más agresivos, por lo que es clasificado por la Organización Mundial de la Salud (OMS) como de grado IV [1], [2]. Este tipo de tumor tiene múltiples mecanismos para evadir los tratamientos y logra invadir rápida y progresivamente el tejido nervioso. En la actualidad, su tratamiento se basa en la combinación entre cirugía, radioterapia y en algunos casos específicos, quimioterapia [2]. En el caso de la radioterapia, se presentan dos grandes retos: el primero es erradicar el tejido tumoral asegurando un daño mínimo al tejido sano circundante; el segundo desafío reside en el fenómeno de la radioresistencia de los tumores, es decir la capacidad del tumor a resistir los efectos destructivos de la radiación ionizante. Por esta razón, se ha explorado la incorporación de agentes radiosensibilizantes que permitan incrementar la dosis recibida en el tumor y evitar el daño en el tejido adyacente [3]. En los últimos años, algunos tipos de nanopartículas han jugado un papel importante en este tipo de aplicaciones debido a sus características particulares como su tamaño, composición, y biocompatibilidad las cuales las hacen capaces de interactuar con radiaciones ionizantes, aumentando la dosis depositada y así potencialmente incrementar la eficiencia de este tipo de terapia [4]. Para el caso específico del uso de nanopartículas como agentes radiosensibilizantes en radioterapia se busca que estas contengan en su composición elementos o especies químicas con un alto número de electrones, lo cual puede generar que en el proceso de irradiación se produzcan emisiones secundarias y por tanto la dosis aplicada en los tumores sea mayor . Los puntos de carbono (PC) son un nuevo tipo de nanopartículas basadas en carbono, atractivos por sus características de biocompatibilidad, biodistribución, propiedades ópticas y su facilidad de síntesis. Adicionalmente, este tipo de nanopartículas presenta la capacidad de agregar en su composición átomos que presenten un alto número atómico [5]. En este trabajo se desarrollaron nanoplataformas basadas en puntos de carbono dopadas con iones lantánidos para su preliminar evaluación como agente radiosensibilizador en el tratamiento de glioblastoma. Los PC son sintetizados por el método de microondas a una temperatura de 200ºC usando urea y ácido cítrico como precursores orgánicos. En el proceso sintéticos se incluyen ácido dietilentriaminopentaacético gadolinio (iii) sal dihidrógeno hidrato y cloruro de iterbio (III) hexahidrato como los precursores de iones lantánidos con el fin de incrementar la nube electrónica que interactuará con los haces de energía ionizante. Las nanoplataformas sintetizadas (PC: PC:Gd3+ y PC:Gd3+,Yb3+) fueron caracterizadas por microscopia de fuerza atómica (AFM, por sus siglas en inglés), potencial Z, espectroscopia de fluorescencia, UV-Vis y de infrarrojo. A continuación, se evaluó el efecto citotóxico en diferentes líneas celulares cancerosas y no cancerosas y cultivos primarios en función de las concentraciones de las nanoplataformas, observando que las PC, PC:Gd3+ y PC:Gd3+,Yb3+ no son citotóxicas en concentraciones menores a 500µg/mL y que en células no cancerosas la viabilidad celular es menor que en las células cancerosas expuestas a los tratamientos. Con el fin de conocer las primeras acercaciones al potencial radiosensibilizador de estas nanoplataformas, líneas celulares y cultivos primarios fueron incubados con estos tratamientos y posteriormente irradiados. Dicho proceso, fue realizado en el Centro de Control de Cáncer a partir de un protocolo de irradiación previo. Después de sembrar las células irradiadas, se analizó su capacidad de proliferación celular obteniendo la curva de fracción de superviviencia para la línea celular U87 y los cultivos primarios de glioma, mostrando una disminución en la fracción de supervivencia de las células con tratamiento (PC y PC:Gd3+) respecto a las células sin el mismo. Concluyendo así, un posible potencial como agente radiosensibilizador en el tratamiento de glioblastoma, por medio del ensayo in vitro. | |
| dc.description.abstract | 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. | |
| dc.format.extent | 76 pp | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.doi | https://doi.org/10.48713/10336_43038 | |
| dc.identifier.uri | https://repository.urosario.edu.co/handle/10336/43038 | |
| dc.language.iso | spa | |
| dc.publisher | Universidad del Rosario | |
| dc.publisher.department | Escuela de Medicina y Ciencias de la Salud | spa |
| dc.publisher.program | Maestría en Ingeniería Biomédica | spa |
| dc.rights | Attribution-NonCommercial-ShareAlike 4.0 International | * |
| dc.rights.accesRights | info:eu-repo/semantics/openAccess | |
| dc.rights.acceso | Abierto (Texto Completo) | |
| dc.rights.licencia | EL AUTOR, manifiesta que la obra objeto de la presente autorización es original y la realizó sin violar o usurpar derechos de autor de terceros, por lo tanto la obra es de exclusiva autoría y tiene la titularidad sobre la misma. | spa |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
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| dc.source.instname | instname:Universidad del Rosario | |
| dc.source.reponame | reponame:Repositorio Institucional EdocUR | |
| dc.subject | Puntos de carbono | |
| dc.subject | Agente radiosensibilizador | |
| dc.subject | Iones lantánidos | |
| dc.subject | Radioterapia | |
| dc.subject | Glioblastoma | |
| dc.subject | Experimentos in vitro | |
| dc.subject.keyword | Carbon dots | |
| dc.subject.keyword | Radiosensitising agent | |
| dc.subject.keyword | Lanthanide ions | |
| dc.subject.keyword | Radiotherapy; Glioblastoma | |
| dc.subject.keyword | In vitro experiments | |
| dc.title | 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 | |
| dc.title.TranslatedTitle | Nanoparticles and radiotherapy: assessing the potential of a nanoplatform doped with lanthanide ions as a radiosensitizing agent in the treatment of glioblastoma in an In Vitro model | |
| dc.type | masterThesis | |
| dc.type.hasVersion | info:eu-repo/semantics/acceptedVersion | |
| dc.type.spa | Tesis de maestría | |
| local.department.report | Escuela de Medicina y Ciencias de la Salud | |
| local.regiones | Bogotá |
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