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Peptide-mediated delivery of therapeutic mRNA in ovarian cancer
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Number of Authors: 92019 (English)In: European journal of pharmaceutics and biopharmaceutics, ISSN 0939-6411, E-ISSN 1873-3441, Vol. 141, p. 180-190Article in journal (Refereed) Published
Abstract [en]

Ovarian cancer is the most lethal gynecological malignancy in the developed world. In spite of intensive research, the mortality has hardly decreased over the past twenty years. This necessitates the exploration of novel therapeutic modalities. Transient protein expression through delivery of mRNA is emerging as a highly promising option. In contrast to gene therapy there is no risk of integration into the genome. Here, we explore the expression of mRNA in models of ovarian cancer of increasing complexity. The cell-penetrating peptide (CPP) PepFect 14 (PF14) was used to formulate CPP-mRNA nanoparticles. Efficient expression of a reporter protein was achieved in two-dimensional tissue cultures and in three-dimensional cancer cell spheroids. PF14 nano particles greatly outperformed a lipid-based transfection agent in vivo, leading to expression in various cell types of tumor associated tissue. Protein expression was restricted to the peritoneal cavity. Messenger RNA expression across different cell types was confirmed in primary ovarian cancer explants. As ovarian cancer is confined to the peritoneal cavity in most cases, the results create the basis for applications in which the tumor microenviron-ment is transiently modified through protein expression.

Place, publisher, year, edition, pages
2019. Vol. 141, p. 180-190
Keywords [en]
Drug delivery, Messenger RNA, Cell-penetrating peptides, Ovarian cancer, Nanomedicine
National Category
Cell Biology Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:su:diva-171695DOI: 10.1016/j.ejpb.2019.05.014ISI: 000476961600018PubMedID: 31103743OAI: oai:DiVA.org:su-171695DiVA, id: diva2:1343809
Available from: 2019-08-19 Created: 2019-08-19 Last updated: 2019-08-19Bibliographically approved

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Gorris, Mark A. J.
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