Modulation of immunity by nanomaterials for the treatment of inflammatory diseases = 면역 조절 약물 전달체에 의한 염증 질환 치료

다국어 초록 (Multilingual Abstract)

Modulation of Immunity by Nanomaterials for the Treatment of Inflammatory Diseases An, Eun-Koung The Graduate School University of Ulsan College of Medical Science Current treatments for inflammatory diseases, such as dexamethasone (Dex) and methotrexate (MTX), often lack targeting specificity. They induce systemic immunosuppression, which can lead to increases in the optimal concentration of the drugs and undesirable side effects. Therefore, the development of targeted therapies is crucial to enhance treatment efficacy while minimizing systemic toxicity. This study aims to develop and evaluate immunomodulatory nanoparticle platforms designed to selectively target activated immune cells and suppress immune responses in inflammatory diseases, including asthma and multi-organ inflammation. Accordingly, two types of hybrid nanoparticles (HNPs) were engineered for the targeted delivery of immunosuppressive molecules and applied to distinct models of inflammation. First, immunosuppressive HNPs (IsHNPs), composed of recombinant murine Programmed Death-Ligand 1 (rmPD-L1) and MTX, were developed to suppress T cell–mediated multi-organ inflammation. Second, dendritic cell (DC)-targeted HNPs were designed with Dex encapsulated in the core and monophosphoryl lipid A (MPLA) coated on the lipid surface (DM-HNPs) to induce tolerogenic DCs (tDCs) and reduce allergic airway inflammation. Both IsHNPs and DM-HNPs promoted the differentiation of regulatory T cells, which directly contributed to the suppression of inflammatory diseases such as multi- organ inflammation and asthma. These results suggest that nanoparticle-based immune modulation is an effective and flexible approach for controlling inflammation in various diseases. This strategy may provide a promising foundation for developing future treatments for immune-related disorders.

목차 (Table of Contents)

• Abstract
• List of Figures
• List of Abbreviations
• Chapter 1. General Introduction 1
• 1.1. Inflammatory Diseases 1
• 1.1.1. Immune Cell Mechanisms in Inflammation 1
• 1.1.2. Overview of Inflammatory Diseases 3
• 1.1.3. Limitations of Current Anti-inflammatory Therapies 5
• 1.2. Nanoparticles as Platforms for Targeted Immunomodulation 6
• 1.3. Research Objectives and Thesis Structure 7
• Chapter 2. Hybrid Nanoparticle (HNP): Therapeutic Trial for Multi-organ Inflammation 10
• 2.1. Introduction 10
• 2.2. Results 11
• 2.3. Discussion 30
• Chapter 3. Hybrid Nanoparticle (HNP): Induction of Tolerogenic Dendritic Cells (tDCs) for Asthma Treatment 32
• 3.1. Introduction 32
• 3.2. Results 34
• 3.3. Discussion 56
• Conclusion 59
• Materials and Methods 60
• Reference 68
• Abstract in Korean 80