Author ORCID Identifier

https://orcid.org/0000-0003-1408-210X

Date Available

11-21-2025

Year of Publication

2025

Document Type

Doctoral Dissertation

Degree Name

Doctor of Philosophy (PhD)

College

Graduate School

Department/School/Program

Clinical and Translational Science

Faculty

Claire Clark

Faculty

Chris Richards

Abstract

Ovarian cancer typically presents at an advanced stage, has a poor prognosis, and is a leading cause of cancer-related deaths in women. Extracellular vesicles (EVs) are cell-derived membrane-bound nanoparticles that function in specific cell-to-cell communication and are under development as novel drug delivery vehicles and modulators of the tumor microenvironment. Artificial cell-derived vesicles (ACDVs) derived from M1 macrophages are able to repolarize M2 macrophages to the M1 phenotype and target tumor cells in in vitro studies.

In this study, we generated engineered EVs (EEVs) by membrane disruption of M1 macrophages (MEVs) in the presence and absence of cisplatin to generate empty MEVs (E-MEVs) and cisplatin-loaded MEVs (C-MEVs) which we tested in an ovarian cancer mouse xenograft model. E-MEVs and C-MEVs exhibited significantly less toxicity and equivalent activity to cisplatin, with improved activity over controls.

This is the first demonstration of the anti-cancer activity of M1 macrophage-derived ACDVs in an ovarian cancer mouse model. E-MEVs and C-MEVs have equivalent activity to cisplatin with less toxicity in an ovarian cancer mouse model, likely a result of MEV tumor specificity. Further development of MEVs for the treatment of ovarian cancer is warranted.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2025.509

Funding Information

This research was supported by NCI T32 CA160003 and Kentucky Network for Innovation & Commercial Grant 30481152221

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