Multi-functional cancer vaccine based on ROS-responsive photoswitching nanocomposites

다국어 초록 (Multilingual Abstract)

Cancer treatment techniques have significantly been advanced in recent decades, but they have a disadvantage of remarkably lowering the immune system in the body. To overcome this issue, immunotherapy is suggested to stimulate the immune system of humans to increase the effectiveness of cancer treatment. Strategies of cancer immunotherapy include immune checkpoint therapy, adoptive cell transfer, and cancer vaccine therapy. Recently, Uric acid (UA), the metabolic end-product of purine metabolism in humans, has been used as an adjuvant in immunotherapy. The crystalline Uric acid (MSU), the leading cause of gout, is known as damage-associated molecular patterns (DAMPs), which are the starting point for triggering the immune effector including dendritic cells and macrophages. In this paper, I devised a photo-switching Nanogel cancer vaccine based on the crystallization of UA, which can be triggered by photodynamic therapy (PDT) via an on-off system for enhancing immune responses. MSU produced after PDT was confirmed using TEM, suggesting that crystallization of UA can be controlled through an on-off system by PDT. The cell penetration efficiency, intracellular distribution, and photo-induced cytotoxicity of the Nanogel were evaluated by in vitro studies on a cancer cell line. Further, the immunogenic efficacy was evaluated by quantitative analysis of DAMPs expression on a cancer cell line.

목차 (Table of Contents)

• Abstract Ⅰ
• Table of Contents Ⅱ
• List of Schemes Ⅴ
• List of Figures Ⅵ
• 1. Introduction
• 1.1. Cancer immunotherapy 2
• 1.1.1. Immunotherapy 2
• 1.1.1.1 Immune checkpoint therapy 5
• 1.1.1.2 Adoptive cell transfer 7
• 1.1.1.3 Cancer vaccines 10
• 1.1.2. Uric acid as DAMPs signal for innate immune response 14
• 1.2 Objective 15
• 2. Experimental Section
• 2.1. General 18
• 2.2. Synthesis of nanogel and Photo-switching nanogel preparation 18
• 2.3. Cell culture 19
• 2.4. Hydrogen peroxide Measurements 20
• 2.5. In vitro Celluar Uptake 21
• 2.6. Determination of In vitro toxicity with WST cell viability assay 22
• 2.7. In vitro Detection of Crucial ICD Biomarkers 22
• 2.7.1. CRT protein cell surface expression analysis 22
• 2.7.2. ATP detection analysis 24
• 2.7.3. HMGB1 protein Western blot analysis 24
• 2.8. In vitro DCs maturation 26
• 3. Results and Discussion
• 3.1. Characterization of Nanogel 28
• 3.2. Photo-switching system of Nanogel on cancer cell 32
• 3.3. DAMPs analysis induced by Nanogel-mediated PDT 38
• 3.4. Maturation of iDCs 47
• 4. Conclusion 49
• References 50