dc.rights.license | CC-BY-NC-ND | |
dc.contributor.advisor | Schiffelers, Raymond | |
dc.contributor.author | Fortuin, Kyra | |
dc.date.accessioned | 2024-11-22T00:02:02Z | |
dc.date.available | 2024-11-22T00:02:02Z | |
dc.date.issued | 2024 | |
dc.identifier.uri | https://studenttheses.uu.nl/handle/20.500.12932/48168 | |
dc.description.abstract | Messenger RNA (mRNA) therapeutics are rapidly emerging as a promising approach for the treatment of a wide range of diseases, including cancer. This is exemplified and reinforced by the recent clinical approval of three nucleic acid-based therapeutics. The type of delivery system plays a pivotal role in the therapeutic efficacy of mRNA-based therapeutics. Among these, lipid nanoparticles (LNPs) have emerged as a highly potential and extensively-studied delivery system. The use of precision-cut tumor slices (PCTS) presents an interesting approach for the evaluation of LNPs in a more native context, as it addresses the translational gap between in vitro and in vivo studies. We present an ex vivo tumor slice platform for the efficient screening of a mRNA-LNP library. Tumor slices were prepared from MC38 tumors grown in C57BL/6J mice and subsequently cultured in vitro. Viability and (endothelial & lymphocyte) cell populations were evaluated over a 48-hour period using a metabolic activity assay, microscopy and flow cytometry. In addition, firefly luciferase (Fluc) mRNA LNPs were generated, characterized and evaluated for efficacy using a 2D in vitro model and the tumor slices. The cultured slices remain viable up to 5 days with endothelial and lymphocyte populations surviving up to 48 hours. Ultimately, tumor slices can be used to successfully screen mRNA LNP libraries. This presents a versatile approach for screening LNP libraries in a reproducible manner within a biologically relevant context, paving the way for more personalized strategies, in for example, cancer therapy. | |
dc.description.sponsorship | Utrecht University | |
dc.language.iso | EN | |
dc.subject | The development of platform that uses precision-cut tumor slices to screen a library of lipid nanoparticles designed for mRNA delivery. | |
dc.title | Developing An Ex Vivo Tumor Slice Platform For Lipid Nanoparticle Screening | |
dc.type.content | Master Thesis | |
dc.rights.accessrights | Open Access | |
dc.subject.keywords | mRNA, cancer, drug delivery, tumor, lipid nanoparticles, LNP, ex vivo models, precision-cut tumor slices, LNP library screening | |
dc.subject.courseuu | Drug Innovation | |
dc.thesis.id | 27042 | |