In this thesis, we start with a general introduction in Chapter 1 to briefly present the state of PDT, immune therapies, and nanotechnology in the field of cancer. PDT is a well-established... Show moreIn this thesis, we start with a general introduction in Chapter 1 to briefly present the state of PDT, immune therapies, and nanotechnology in the field of cancer. PDT is a well-established approach in superficial cancer treatment. The aim of my Ph.D. research work has been to improve therapeutic responses in solid tumors by novel combinatorial strategies based on PDT and the utilization of nanotechnology. Insights and concepts in these works are expected to help to design personalized therapeutic interventions in cancer progression. In Chapter 2, we focused on the combination of PDT with a stimulator of interferon genes (STING) agonist: ADU-S100. We investigated the anti-tumor efficiency and survival time after this combined treatment in colon tumor mice models. We found that ADU-S100 post-PDT treatment could enhance PDT-induced inflammation and immune responses, which lead to abscopal effects in a distal untreated tumor. The combination also protected cured mice from tumor recurrence through memory T cell anti-tumor immune responses with high probability. In Chapter 3, we found that PDT in combination with viral core particles could prime systematic immune responses and serum antibody intensity to against colon cancer process in MC38 tumor-bearing mice. In Chapter 4, we reviewed the current challenges facing the combination of PDT and multiple cancer treatment options based on current published literature. We highlighted the opportunities of nanoparticle-based PDT in cancer therapies. In Chapter 5, we investigated how hydrogel-supported near-infrared (NIR) -PDT with improved therapy potential in tumor-bearing mice by combining it with immune checkpoint inhibitors. In addition to the improved tumor growth inhibitory effects and prolonged survival time, immune mechanisms were also studied. We found that hydrogel-supported NIR-PDT by multi-stimulation could induce a higher level of lymphocytes in the circulating blood and increased lymphocytes infiltration into tumor site. A general discussion of overall data observed in this work, and clinical and research prospects related to this thesis are provided in Chapter 6. Show less
In this thesis, the effects of a new form of immunotherapy was investigated and studied how it can be used against different types of cancers. The investigated immunotherapy is based on injecting... Show moreIn this thesis, the effects of a new form of immunotherapy was investigated and studied how it can be used against different types of cancers. The investigated immunotherapy is based on injecting nanoparticles loaded with various immunologically active molecules (immunomodulatory nanoparticles) that can modulate the immune system to attack cancer cells more efficiently. The effectiveness of this immunomodulatory nanoparticles have been studied on different mouse cancer models and investigated as a single treatment or in combination with other known therapies, such as chemotherapy, therapeutic cancer vaccination, or photodynamic therapy. Show less
In cancer treatment, nanomedicines may be employed in an attempt to improve the tumor localization of antineoplastic drugs e.g. immunotherapeutic agents either through passive or active targeting,... Show moreIn cancer treatment, nanomedicines may be employed in an attempt to improve the tumor localization of antineoplastic drugs e.g. immunotherapeutic agents either through passive or active targeting, thereby potentially enhancing therapeutic effect and reducing undesired off-target effects. However, a large number of administrated nanocarriers often fail to reach the tumor area. In the present study, we show that photodynamic therapy (PDT) enhances the tumor accumulation of systemically administered lipid-PEG layer coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP). Intravital microscopy and histological analysis of the tumor area reveal that the tumor vasculature was disrupted after PDT, disturbing blood flow and coinciding with entrapment of nanocarriers in the tumor area. We observed that the nanoparticles accumulating after treatment do not confine to specific locations within the tumor, but rather localize to various cells present throughout the tumor area. Finally, we show by flow cytometry that NP accumulation occurred mostly in immune cells of the myeloid lineage present in the tumor microenvironment (TME) as well as in tumor cells, albeit to a lower extent. These data expose opportunities for combination treatments of clinical PDT with NP-based immunotherapy to modulate the TME and improve antitumor immune responses. Show less
