Design and Production of a Nanomedicine with Improved Tissue Permeability within a Tumor
- 주제어 (키워드) Nanoparticles , Surface Modification , Tissue Penetration
- 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/000000078985
- UCI I804:11029-000000078985
- 본문언어 영어
- 저작권 서강대학교 논문은 저작권 보호를 받습니다.
초록 (요약문)
Nanoparticles hold significant potential for biomedical applications, but their effectiveness is hindered by cellular barriers, such as the plasma membrane and endosomal compartment, as well as low tissue permeability, particularly in the complex extracellular matrix of the tumor microenvironment. This results in suboptimal chemotherapeutic efficacy due to nanoparticles primarily localizing in the perivascular area and tumor periphery. Thus, improving nanoparticle delivery to deep tissues remains a critical challenge. In this study, we developed phospholipid nanotube-modified protein nanoparticles (LT-NPs) to enhance delivery to cancer cells and deep tumor regions. Human serum albumin nanoparticles were fabricated using an ethanol desolvation method and cross-linked with disulfide bonds. Phospholipid nanotube structures were induced on the surface of these nanoparticles via self-assembly. The cellular uptake efficiency of LT-NPs was assessed through fluorescence microscopy and flow cytometry, while tissue penetrability was evaluated using 300μm-sized spheroids analyzed with confocal microscopy. The LT-NPs demonstrated significantly enhanced tissue penetration and intracellular delivery capabilities, with a more than 50-fold increase in intracellular uptake compared to unmodified nanoparticles. LT-NPs were found in substantial amounts deep within the spheroids, unlike the unmodified nanoparticles, confirming that surface modification with phospholipid nanotubes can significantly improve nanoparticle cell and tissue permeability.
more목차
1. Introduction 1
1.1. Background 1
1.2. Recent developments of tumor permeable nanoparticles 7
1.3. Hypothesis 16
2. Materials and Methods 19
2.1. Materials 19
2.2. Fabrication of Human Serum Albumin (HSA) NPs 19
2.3. Fabrication of Lipid-Nanotube Induced Nanoparticles (LT-NPs) 20
2.4. In vitro cellular uptake efficiency of LT-NPs 21
2.5. In vitro cell uptake efficiency of LT-NPs on spheroid cell 22
2.6. Verification of Lipoprotein-like Delivery of LT-NPs 24
2.7. In Vivo Biodistribution of NPs and LT-NPs 24
2.8. Fabrication of doxorubicin loaded albumin nanoparticles 25
2.9. In vitro cytotoxicity profile of doxorubicin loaded LT-NPs 26
3. Results and Discussion 28
3.1. Characterization of LT-NPs 28
3.2. Enhanced cellular uptake of LT-NPs on cellular monolayer 31
3.3 Enhanced cellular uptake of LT-NPs on spheroid model 35
3.4 Lipoprotein-like delivery of LT-NPs 39
3.5. In Vivo Biodistribution Analysis: Enhanced Tumor Penetration and Retention of LT-NPs 43
3.6 Characterization and evaluation of Dox-NPs and Dox-LT-NPs 47
4. Conclusion 51
5. References 53
