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dc.rights.licenseCC-BY-NC-ND
dc.contributor.advisorSchiffelers, Raymond
dc.contributor.authorFortuin, Kyra
dc.date.accessioned2024-11-22T00:02:02Z
dc.date.available2024-11-22T00:02:02Z
dc.date.issued2024
dc.identifier.urihttps://studenttheses.uu.nl/handle/20.500.12932/48168
dc.description.abstractMessenger 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.sponsorshipUtrecht University
dc.language.isoEN
dc.subjectThe development of platform that uses precision-cut tumor slices to screen a library of lipid nanoparticles designed for mRNA delivery.
dc.titleDeveloping An Ex Vivo Tumor Slice Platform For Lipid Nanoparticle Screening
dc.type.contentMaster Thesis
dc.rights.accessrightsOpen Access
dc.subject.keywordsmRNA, cancer, drug delivery, tumor, lipid nanoparticles, LNP, ex vivo models, precision-cut tumor slices, LNP library screening
dc.subject.courseuuDrug Innovation
dc.thesis.id27042


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