Development and functionalization of gold nanoparticles with silica coating for application in cancer therapy

• Autor(a) principal: Gonçalves, Ariana Soraia Carreira
• Data de Publicação: 2020
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.6/10546
• topic: Ir780; Cancro; Gel; Nanopartículas de Ouro Com Revestimento de Sílica; Peg-Ch3.; Terapia Fototérmica; Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas

Cancer is one of the leading causes of death worldwide and its incidence is expected to continue to increase over the next few decades. Such is explained by the non-specific toxicity and reduced therapeutic efficacy displayed by conventional treatments currently used in the clinic, namely surgery, chemotherapy, and radiotherapy. Particularly, chemotherapeutic agents are rapidly degraded and present a reduced solubility and selectivity to cancer cells. Among the new therapeutic approaches that have been developed, the application of nanomaterials capable of mediating a photothermal effect (i.e. increasing the temperature in response to a light stimulus with a specific wavelength), to induce the cancer cell deaths have been gaining increased attention. Among the several nanomaterials applied in photothermal therapy (PTT), gold core silica shell (AuMSS) nanoparticles presented excellent physicochemical properties that allow their application as photothermal and drug delivery agents. Different parameters of the gold core (e.g. size, shape) can be optimized to improve the photothermal capacity of these nanoparticles, and consequently their therapeutic efficacy. Additionally, the combination of AuMSS nanoparticles with other materials and molecules can also improve their photothermal effectiveness. However, despite the high therapeutic potential of AuMSS nanoparticles, their clinical application is hampered by their reduced circulation time in the bloodstream and lack of specificity to the tumoral tissue. Taking this into account, the research work developed during the second year of my MSc aimed to develop a new surface functionalization for rod-shaped AuMSS nanoparticles, based in biofunctional polymers to increase both its half-life in the bloodstream and internalization by cancer cells. For this purpose, the rod-shaped AuMSS nanoparticles were chemically modified with Polyethyleneglycol methyl ether (PEG-CH3) and Gelatin (GEL). The PEG-CH3 was chosen due to its amphiphilic nature and high solubility, which reduces the protein adsorption on the nanoparticles’ surface and consequently increases its blood circulation time. On the other hand, GEL is a natural polymer that contains arginine-glycine-aspartic acid (RGD) amino acid sequences with specificity for receptors overexpressed in cancer cells. Simultaneously, the encapsulation of IR780 was also tested for the first time in AuMSS nanoparticles to increase the photothermal and photodynamic capacity, and consequently its therapeutic potential. The obtained results demonstrated that the functionalization of rod-shaped AuMSS nanoparticles with GEL and PEG-CH3 polymers led to a neutralization of the surface charge from -23 to -7.46 mV. The successful incorporation of the polymers on nanoparticles surface was also confirmed by thermogravimetric analysis (TGA) and by Fourier transform infrared spectroscopy (FTIR). The in vitro studies demonstrated the biocompatibility of the different nanoformulations when in contact with cancer cells (cervical cancer) and healthy cells (fibroblasts) up to the maximum tested concentration of 200 µg.mL-1 . Additionally, the AuMSS functionalization with GEL increased their internalization by cancer cells without affecting their photothermal capacity. Otherwise, it was also observed that the encapsulation of IR780 resulted in an enhanced photothermal capacity of AuMSS/T-PEG-CH3/T-GEL nanoparticles and increased the generation of reactive oxygen species (ROS) upon irradiation with a NIR laser. Finally, the AuMSS/T-PEG-CH3/T-GEL nanoparticles were capable of effectively inducing the death of cancer cells. In summary, the obtained results confirm the successful functionalization of AuMSS nanoparticles with the GEL and PEG-CH3. Additionally, the potential of the AuMSS/IR780 combination was also demonstrated, where this nanosystem can simultaneously perform PTT and photodynamic therapy (PDT), which translates to an enhanced anticancer capacity.