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Publication year
2019Source
European Journal of Pharmaceutics and Biopharmaceutics, 141, (2019), pp. 180-190ISSN
Publication type
Article / Letter to editor

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Organization
Biochemistry (UMC)
Gynaecology
Tumorimmunology
Laboratory Medicine
Journal title
European Journal of Pharmaceutics and Biopharmaceutics
Volume
vol. 141
Page start
p. 180
Page end
p. 190
Subject
Radboudumc 17: Women's cancers RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 19: Nanomedicine RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 2: Cancer development and immune defence RIMLS: Radboud Institute for Molecular Life SciencesAbstract
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 nanoparticles 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 microenvironment is transiently modified through protein expression.
This item appears in the following Collection(s)
- Academic publications [227881]
- Electronic publications [107344]
- Faculty of Medical Sciences [86219]
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