Micro-Syringe chip-guided intratumoral administration of photosensitizer lipid nanoparticles for targeted anticancer immunotherapy
- 주제어 (키워드) Nanoparticles , Photodynamic therapy (PDT) , Photosensitizer-prodrug , photochemotherapy , cancer immunotherapy , immune checkpoint blockade , Lipid nanoparticles
- 발행기관 서강대학교 일반대학원
- 지도교수 김현철
- 발행년도 2024
- 학위수여년월 2024. 8
- 학위명 석사
- 학과 및 전공 일반대학원 화공생명공학과
- 실제 URI http://www.dcollection.net/handler/sogang/000000079172
- UCI I804:11029-000000079172
- 본문언어 영어
- 저작권 서강대학교 논문은 저작권 보호를 받습니다.
초록 (요약문)
Nano-scale drug delivery systems have been extensively studied as a promising technology to improve the targeted delivery of anticancer agents to tumors, leveraging their passive targeting characteristics. However, systemic administration has shown limited advancements, mainly due to the significant drawback of severe side effects associated with systemic circulation post intravenous injection. To address this challenge, we employed micro-syringe chip to achieve localized tumor-specific action with minimal invasiveness. Furthermore, we developed photo responsive nanostructures using appropriate liposomal components to enhance accumulation efficiency and conducted immunotherapy with suitable light irradiation. This approach is elaborated in the paper as a promising strategy to alleviate adverse effects while maximizing therapeutic efficacy against cancer.
more목차
1. Introduction 1
2. Materials and Methods 4
2-1. Materials 4
2-2. Synthesis of Photosensitizer cathepsin B-cleavable prodrugs 5
2-3. Formation and characterization of Photosensitizer prodrug nanoparticles 6
2-4. Formation and characterization of Lipid Photosensitizer prodrug nanoparticles (LNP) 7
2-5. In vitro Cellular uptake imaging 8
2-6. In vitro cytotoxicity analysis with Apoptosis 9
2-7 in vitro Western blot assay 10
2-8. In vitro Reactive oxygen species (ROS) assay 11
2-9. In vitro DAMP (Damage-associated molecular pattern) signals 11
2-10. In vivo intratumoral delivery of Photo-Nanoparticles and Photo-Lipid Nanoparticles to tumor-bearing mice using a micro-syringe chip 12
2-11. In vivo Tumor Inhibition and Immune Response with therapeutic efficacy of Micro-syringe chip-administered Photo-nanoparticles and Photo-lipid nanoparticles tumorbearing mice 13
3. Results and Discussions 16
3-1. The application and elucidation of the Micro-syringe chip, including its injection method, in cancer treatment 16
3-2. Preparation of light-sensitive cathepsin B-cleavable prodrug nanoparticles 19
3-3. Characterizations of Implantable MSC with Photo- Lipid nanoparticles 26
3-4. In Vitro Photo-nanoparticles and Photo-Lipid nanoparticles against cancer cells 34
3-5. In Vivo Biodistribution and therapeutic efficacy of Photo-nanoparticle or Photo- Lipid nanoparticles in tumor-bearing mice 42
4. Conclusion 53
5. References 54