Towards photodynamic therapy with ionising radiation: nanoparticle-mediated singlet oxygen generation and quantification

Photodynamic therapy (PDT) is a clinically approved procedure for the treatment of cancer and other health conditions by using singlet oxygen, a highly reactive oxygen generated from a photosensitizer drug upon photoactivation. Certain limitations exist with the current photosensitizers such as poor solubility in biological media, lack of selective accumulation and minimal absorption in the tissue transparency window. Also, the limited tissue penetration of light in the absorption band of most photosensitizers makes the PDT unsuitable for deep tissue cancer treatments. To improve the performance of these photosynthesizers in deep tissue PDT, nanoparticles are introduced eitheras a carrier, as the photosynthesizer itselfor as an energy transducer. The X-ray / gamma ray activated nanoparticles can trigger the photosensitizer drug to generate singlet oxygen. Additionally, inorganic nanoparticles may interact more strongly with X-ray and/or gamma rays rather than the tissue, allowing the effects of radiation to be concentrated near the nanoparticle surface. Furthermore, nanoparticles can also be molecularly targeted to cancer cells. The main goal of this PhD project is to enhance the singlet oxygen generation capability of the photosensitizer by conjunction with different nanoparticles which enhances selectivity to enable deep tissue PDT treatment. This thesis adopts the "thesis-by-publication" approach and it is preceded by a brief introduction chapter mentioning the thesis outline, followed by two chapters regarding the PDT review and characterisation techniques, one conclusion chapter and four results chapters containing my publications and manuscripts (all first author papers, one published in Journal of Nanoparticles Research, one published in Journal of Photochemistry and Photobiology A: Chemistry, one published in Nature Scientific Reports, one in manuscript form ready for submission in Journal of Advanced Healthcare Materials).