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Cancer therapy has been a prominent topic of study for several decades by the medical, academic and pharmaceutical industry communities. In particular, skin cancer has assumed high relevance due to the degradation of the ozone layer and consequent increase in human exposure to UV radiation that induces genetic mutations. The focus has been on novel treatments and agents that increase the effectiveness of therapies, destroying the tumour cells while sparing the surrounding healthy tissues. The aim of this work was to analyse the damage driven by UV and visible radiation in relevant biological molecules and to understand how to enhance the radiation damage, namely by adding AuNPs to illuminated samples. A combination of different techniques represents an innovative and promising approach to be explored. The work described in this thesis addresses this methodology from two different standpoints: 1) the degradation of DNA molecules after exposure to UVC radiation, to design a biological dosimeter that effectively demonstrates and measures the radiation induced damage; and 2) the effects of visible light laser radiation (Nd:YAG ) on halogenated nucleobases and plasmid DNA conjugated with gold nanoparticles (AuNPs). The radiation damage induced in biological molecules was evaluated by spectroscopic techniques, microscopies, electrophoresis and measuring the production of free radicals and reactive species during water photolysis. This thesis demonstrates the potential of such a combined chemo-phototherapy methodology and the effectiveness of AuNPs in such treatment. Moreover, we have proven damage enhancement with the combination of pulsed laser and AuNPs in relevant biological molecules. The new findings of the interaction of Nd:YAG light with AuNPs and DNA molecules point to their efficacy and applicability in melanoma therapy. However, additional in vitro studies with cell lines, followed by in vivo assays, should be conducted, investigating whether the benefits surpass the possible damage caused in the vicinity of the illuminated area. A terapia de cancro, dos mais variados tipos de tumores e possíveis combinações de tratamentos, tem sido tema de estudo há várias décadas por parte das comunidades médica, académica e indústria farmacêutica. Nomeadamente o cancro de pele tem assumido elevada relevância devido à degradação da camada de ozono e consequente exposição a radiações que induzem mutações genéticas. Novos tratamentos, agentes que aumentem a eficácia das terapias com menor dano de células saudáveis, e a conjugação destes dois, representam novas e promissoras técnicas a ser exploradas. Assim, o uso de nanopartículas de metais nobres e a terapia com fotões são práticas cada vez mais procuradas na terapia do cancro de pele. Este trabalho estuda esta problemática com duas abordagens diferentes, nomeadamente 1) estudos da degradação de moléculas de ADN após a exposição a radiação UVC, com o objectivo de conceber um dosímetro biológico que demonstre de uma forma eficaz os danos induzidos; e 2) investigação dos efeitos em nucleobases halogenadas e plasmídeo de ADN da conjugação de nanopartículas de ouro (AuNPs) e radiação no espectro do visível com um feixe de luz a 532 nm produzido por um laser pulsado (Nd:YAG). Os danos induzidos nas moléculas biológicas referidas anteriormente foram avaliados recorrendo a técnicas de espectroscopia, caracterização por microscopia, separação molecular por electroforese e avaliação da produção de radicais livres e espécies reactivas formadas durante a fotólise da água. Este trabalho demonstrou o potencial da quimio-fototerapia combinada estudada, e comprovou eficácia das AuNPs. As novas descobertas da interação de AuNPs com Nd:YAg e moléculas de ADN apontam para a sua eficácia e aplicabilidade em tratamentos de melanomas, contudo mais estudos in vitro com linhas celulares, seguidos por ensaios in vivo devem ser realizados, investigando se os benefícios são superiores aos possíveis danos causados na proximidade da área iluminada.

A wide range of nanoparticles (NPs), composed of different elements and their compounds, are being developed by several groups as possible radiosensitisers, with some already in clinical trials. However, no systematic experimental survey of the clinical X-ray radiosensitising potential of different element NPs has been made. In this thesis, a direct comparison is made through the irradiation-induced (10 Gy of 6 MeV X-ray photon) production of reactive oxygen species (ROS) such as hydroxyl radicals, superoxide anion radicals and singlet oxygen in aqueous solutions of the different metal oxide NPs. Also, cancer cell and DNA damage due to these NPs is studied under irradiation conditions. The results of this thesis showed that without any X-rays, several NPs produced different radicals. Furthermore, NPs such as vanadium oxide (V2O5) produced a significant amount of radicals compared to water and to the other types of NPs when irradiated with 10 Gy of 6 MeV X-rays and NPs such as copper oxide (CuO) showed significant cell and DNA damage that is not related to the production of ROS. Beyond identifying promising metal oxide NPs radiosensitisers, these results have shown evidence that the chemical and biological effects of these NPs are also present in the mode of action of these radiosensitisers challenging the pure physical radio-enhancement concept.