PHOTODYNAMIC THERAPIES AND ETHANOL ABLATION FOR UNRESECTABLE TUMORS AND ASSAY DEVELOPMENT

Abstract

Many cancers pose significant challenges due to their low survival rates, especially when tumors are deemed unresectable. These tumors are either spread diffusely or located in areas that make surgical intervention risky or impossible. This dissertation addresses innovative approaches to treating unresectable cancers, including solid and peritoneal metastasis, by using photodynamic therapy (PDT)-based combination therapy. The initial section of the dissertation reviews the atypical administration routes of photosensitizers, particularly through intratumoral, intraperitoneal, and intra-arterial injections. Next, the study evaluates the Light-Activatable Sustained-Exposure Ethanol Injection Technology (LASEIT)’s performance in xenograft models of hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC). The photochemical properties of LASEIT in tissue-mimicking agarose, ex vivo swine liver, and xenograft animal models were confirmed, demonstrating its ability to maintain fluorescence and extend light propagation. Tumor-killing efficacy was shown in both single- and multi-cycle treatments, positioning LASEIT as a promising alternative for solid tumor therapy. The dissertation also investigates the potential of NanoVP, a carrier-free photosensitizer, for the treatment of peritoneal cancers. We confirmed that NanoVP was detectable in swine peritoneal organs using the ML7710 medical laser system, indicating its potential for personalized PDT in the future. However, we also discovered challenges in detecting photobleaching in pigmented organs like the spleen and liver. Finally, the dissertation employs quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) to quantify peritoneal cancer cell metastasis in a xenograft ovarian cancer model, confirming the technique’s reliability in detecting low numbers of human cells in mouse tissues.