Enhancing photodynamic therapy of refractory solid cancers

Photodynamic therapy (PDT) is based on the activation of a photosensitizer by (laser) light to locally produce highly destructive reactive oxygen species. When employed for cancer treatment, PDT is able to induce tumor cell death, microvascular damage, and an anti-tumor immune response. All these factors contribute to tumor destruction. Although PDT is successfully applied for a variety of tumor types, PDT yields promising yet unsatisfactory results in non-resectable perihilar cholangiocarcinoma patients. This is partly due to the use of suboptimal photosensitizers and the activation of survival signaling in PDT-subjected but sublethally afflicted tumor cells. Consequently, the aim of this research was to design a novel PDT strategy to treat these patients in a selective and effective manner. The first part of this thesis focuses on the incorporation of a photosensitizer with superior photochemical properties into a multitargeting liposomal delivery system. The second part analyzes the survival response in PDT-treated tumor cells and in the third part of this thesis we pharmacologically intervened in survival programs to improve therapeutic efficacy