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Updated: Jan 24, 2026
In vivo Imaging and Therapeutic Treatments in an Orthotopic Mouse Model of Ovarian Cancer
Published on: August 17, 2010
Peptide-mediated delivery of therapeutic mRNA in ovarian cancer
Dirk van den Brand1, Mark A J Gorris2, Alexander H van Asbeck3
1Dept. of Biochemistry, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Geert Grooteplein 28, 6525 GA Nijmegen, the Netherlands; Dept. of Obstetrics and Gynaecology, Radboud University Medical Center, Geert Grooteplein 10, 6525 GA Nijmegen, the Netherlands.
Abstract:
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.
Insights
Messenger RNA (mRNA) delivery using cell-penetrating peptide (CPP) nanoparticles shows promise for ovarian cancer therapy. This approach enables transient protein expression within the tumor microenvironment, offering a novel therapeutic avenue.
Area of Science:
- Oncology
- Biotechnology
- Nanomedicine
Background:
- Ovarian cancer remains a leading cause of gynecological cancer mortality with limited therapeutic advancements.
- Novel strategies are crucial for improving treatment outcomes in ovarian cancer.
- Messenger RNA (mRNA) delivery presents a promising alternative to gene therapy due to its transient nature and lack of genomic integration.
Purpose of the Study:
- To investigate the efficacy of cell-penetrating peptide (CPP) formulated mRNA nanoparticles for protein expression in ovarian cancer models.
- To evaluate the performance of CPP-mRNA nanoparticles compared to traditional transfection agents.
- To establish a foundation for transient protein expression-based therapies targeting the ovarian cancer tumor microenvironment.
Main Methods:
- Formulation of CPP-mRNA nanoparticles using PepFect 14 (PF14).
- Assessment of reporter protein expression in 2D cultures and 3D cancer spheroids.
- In vivo evaluation of PF14 nanoparticles in ovarian cancer models.
- Analysis of mRNA expression in primary ovarian cancer explants.
Main Results:
- Efficient reporter protein expression was achieved in both 2D and 3D ovarian cancer models.
- PF14 nanoparticles demonstrated superior transfection efficiency compared to a lipid-based agent in vivo.
- Protein expression was localized to the peritoneal cavity, consistent with ovarian cancer progression.
- Successful mRNA expression was confirmed across diverse cell types within primary ovarian cancer explants.
Conclusions:
- CPP-mRNA nanoparticles are effective for transient protein expression in ovarian cancer models.
- This technology offers a potential platform for modifying the tumor microenvironment in ovarian cancer.
- The localized expression within the peritoneal cavity is advantageous for ovarian cancer therapeutic applications.
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