University of Twente Student Theses
Active targeting of the extracellular matrix in the tumor microenvironment using novel collagen-binding peptides
Veerman, Devin (2022) Active targeting of the extracellular matrix in the tumor microenvironment using novel collagen-binding peptides.
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| Full Text Status: | Access to this publication is restricted |
| Embargo date: | 31 January 2025 |
| Abstract: | Cancer, or malignant tumor, is the second leading cause of death worldwide. During tumor progression, cancer cells actively act on and restructure their surrounding tissue, creating what is known as the tumor stroma or tumor microenvironment (TME). The TME supports tumors to survive, progress and become resistant to therapies. Adenocarcinomas, such as pancreatic ductal adenocarcinoma (PDAC), are known for its high degree of desmoplasia resulting in the increased deposition of extracellular matrix (ECM) which is mainly comprised of collagens type I and III. Moreover, the increase in collagen type III appears to be more tumor-specific as compared to collagen type I. Collagen as a therapeutic target to deliver therapeutic agents to the fibrotic TME is a promising but rarely investigated strategy. While most researchers focus on targeting collagen type I, targeting collagen type III is a novel approach to target desmoplastic tumors. In this thesis, a novel collagen-binding peptide (CN3) was utilized and subjected to enzyme-linked immunosorbent assays (ELISAs) to evaluate binding affinity to various proteins of the ECM. Then, in vitro and ex vivo experiments were conducted to visualize binding of the peptide using collagen-producing cells, and murine PDAC models, respectively. Thereafter, the peptide was conjugated to liposomes to establish collagen-targeted nanocarriers. Liposomes were characterized, evaluated for binding affinity, and used for uptake experiments. We found that first, the CN3-peptide showed increased binding affinity to collagen type III as compared to collagen type I. Furthermore, in vitro and ex vivo studies revealed colocalization of the CN3-peptide with cell-produced collagen. Yet, the CN3-peptide showed unspecific binding which might be related to its properties. Next, the CN3-peptide could be coupled to the liposomes and showed increased binding affinity to both collagen types I and III as compared to the control. Uptake studies did not reveal a difference between between CN3-liposomes and control liposomes. Yet, data showed that the uptake studies were far from optimized. In conclusion, we developed novel collagen-binding nanoparticles that could be used to target desmoplastic tumors. Further studies should focus on improving peptides’ properties and binding specificity and evaluate the nanocarriers in more advanced models. |
| Item Type: | Essay (Master) |
| Faculty: | TNW: Science and Technology |
| Subject: | 42 biology, 44 medicine |
| Programme: | Biomedical Engineering MSc (66226) |
| Link to this item: | https://purl.utwente.nl/essays/89568 |
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