Interactions Between Targeted Nanoparticle-Delivered Chemotherapy and Immune Checkpoint Regulation in Ovarian Cancer Cells
- 주제(키워드) Ovarian Cancer , Lipid Nanoparticles , Targeting , Topoisomerase I Inhibitor , PD-L1 Inhibitor , Cell Viability Assay
- 주제(DDC) 651.1
- 발행기관 아주대학교 일반대학원
- 지도교수 Hyo-Eon Jin
- 발행년도 2026
- 학위수여년월 2026. 2
- 학위명 석사
- 학과 및 전공 일반대학원 바이오헬스규제과학과
- 실제URI http://www.dcollection.net/handler/ajou/000000035903
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Ovarian cancer is associated with a high rate of recurrence and limited efficacy of conventional chemotherapy. Topoisomerase I inhibitors exhibit cytotoxic activity against ovarian cancer cells; however, their use is limited by formulation-related issues such as low solubility and instability. Lipid nanoparticle (LNP) systems have been investigated as a means to improve intracellular drug delivery. In this study, an LNP formulation encapsulating a topoisomerase I inhibitor was prepared and surface-modified with a peptide targeting a tumor-associated antigen overexpressed in ovarian cancer cells. The aims of this study were to optimize the formulation with respect to particle characteristics and encapsulation efficiency, to characterize its physicochemical properties, and to evaluate its in vitro cytotoxic activity in the presence or absence of a small-molecule PD-L1 inhibitor. The optimized formulation, designated LNP-D-T, exhibited a mean particle size of 149.7 ± 11.6 nm and an encapsulation efficiency of 91.51 ± 5.25%. In vitro cytotoxicity assays conducted in NIH:OVCAR-3 cells showed that LNP-D-T resulted in lower cell survival compared with a non-targeted LNP formulation and the free drug after 72 hours of treatment. Western blot analysis indicated an increase in PD-L1 expression following treatment with the topoisomerase I inhibitor over a 24–72 hour period. Under PBMC co-culture conditions, treatment with LNP-D-T was associated with reduced cell viability, and additional treatment with a PD-L1 inhibitor resulted in a further decrease in cell viability under the experimental conditions used in this study. In summary, this study describes the preparation and in vitro evaluation of a peptide- targeted LNP formulation for the delivery of a topoisomerase I inhibitor in ovarian cancer cells. The findings provide basic formulation and in vitro activity data that may be useful for subsequent studies. _____________________________________________________________ Keywords: Ovarian Cancer, Lipid Nanoparticles, Targeting, Topoisomerase I Inhibitor, PD-L1 Inhibitor, Cell Viability Assay
more목차
1. Introduction 1
1.1 Epidemiology and Clinical Significance of Ovarian Cancer 1
1.2 Limitations of Chemotherapy and Immune Evasion Mechanisms 2
1.3 Immunotherapy and the PD-1/PD-L1 Immune Checkpoint Pathway 4
1.4 The Synergistic Mechanism of Chemotherapy and Immunotherapy 6
1.5 Innovation in Drug Delivery Systems Using Lipid Nanoparticles 7
2. Materials and Methods 10
2.1 Materials 10
2.2 Preparation of Drug-Loaded Lipid Nanoparticles 10
2.3 Cell Culture 12
2.4 Western Blot Analysis 12
2.5 Cytotoxicity Assay (MTT Assay) 14
2.6 PBMC Co-culture Cytotoxicity Assay 14
3. Results 16
3.1 Physicochemical Characterization of Lipid Nanoparticles 16
3.2 Expression of Target Antigen and Immune Checkpoint Ligand in Ovarian Cancer Cell Lines 19
3.3 Upregulation of PD-L1 Expression Following Topoisomerase I Inhibitor Treatment 21
3.4 Evaluation of In Vitro Cytotoxicity 23
3.5 Synergistic Cytotoxicity in Co-culture with PBMC Against 26
4. Discussion 28
5. Conclusion 31
References 32
국문요약 38
