Development of multifunctional fucoidan-coated nanoparticles for combined cancer therapy

• Autor(a) principal: Gonçalves, Joana Daniela Ferreira
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/25897
• topic: Magnetic hyperthermia; Magnetic nanoparticles; Magnetite; Co-precipitation; Fucoidan

Magnetic nanoparticles, namely magnetite nanoparticles (NP) have been subject of research and development for application in the biomedical field, especially in magnetic hyperthermia as a therapy for cancer. NPs are often coated with various materials such as silicates and natural or synthetic polymers such as chitosan or polyethylene glycol (PEG), in order to improve biocompatibility but also to enhance their colloidal stability. Fucoidan is a polysaccharide extensively studied for biomedical applications mainly due to its biocompatibility and antitumor properties. In this work, NP of magnetite coated with fucoidan are developed and evaluated for the application in magnetic hyperthermia for cancer treatment, combining magnetic hyperthermia therapy with the antitumor properties of fucoidan. The NP are synthesized by the co-precipitation method at room temperature and, afterwards, subjected to a hydrothermal treatment with different time (1, 2, and 3 h) and temperature (150 or 200 ºC) conditions. The coating of the particles with fucoidan are performed using two methodologies: i) after their synthesis (post-synthesis coating) and ii) simultaneously with the synthesis (in situ coating). Different concentrations of fucoidan are tested in the post-synthesis coatings to evaluate their influence on the physicochemical properties and the thermal efficiency of NP. In the in situ coating syntheses, in addition to evaluating the effect of different concentrations of fucoidan, the influence of the reaction temperature on the functionalization of the NP surface are also studied. NP are characterized in terms of crystallinity and particle size, specific surface area, morphology, colloidal stability and thermal efficiency. In general, NPs synthesized and coated with fucoidan have nearly round shape morphology, and in terms of size NPs with smaller size exhibited a larger surface area. The hydrothermal treatment promoted the increase of NP crystallinity and size as a function of the time and temperature of the hydrothermal treatment. There is also an increase in polydispersity which resulted in a decrease in heating efficiency by hyperthermia. The coating with fucoidan showed to improve the colloidal stability and, consequently, the thermal efficiency due to the reduction of the interactions between the NP. For the synthesis of NP by co-precipitation and post-synthesis coated, better results were obtained in terms of stability, due to the fact that the NPs obtained in situ are smaller and have a greater tendency to agglomerate. The sample giving the best results in the heat release was the one synthesized by co-precipitation at room temperature and coated post-synthesis with a concentration of fucoidan of 2 mg/mL, presenting an Intrinsic Loss Power (ILP) of 2.6 nHm2/kg, which according to literature is considered sufficient in terms of thermal efficiency (2 to 4 nHm2/kg). In addition, this sample had an average size within the recommended range for introduction into the body (less than 20 nm) mainly for its potential application in magnetic hyperthermia. However, NP synthesized and coated simultaneously with 2 mg/mL fucoidan also showed a high thermal efficiency (1.7 nHm2/kg) and its preparation process is simpler. For all of the above described, the results obtained in this work demonstrated that NP of magnetite coated with fucoidan have potential for application in magnetic hyperthermia and may also have, as a consequence of the intrinsic characteristics of fucoidan, antitumoral properties, which allow to potentiate the cancer treatment