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Scalable Engineering of Bio-Manufactured Extracellular Vesicles for Selective Delivery in Ovarian Cancer
Nihar Godbole1,2, Andrew Lai1,2, Alexander Quinn3,4
1Translational Extracellular Vesicles in Obstetrics and Gynae-Oncology Group, Frazer Institute, Faculty of Health Medicine and Behavioural Sciences, Royal Brisbane and Women's Hospital, The University of Queensland, Herston, Queensland, Australia.
Researchers engineered extracellular vesicles (EVs) for targeted ovarian cancer delivery. These engineered EVs (eEVs) carrying bioluminescent cargo accumulate in EphB4-positive tumors, enabling non-invasive tracking and reporting drug distribution for precision medicine.
Area of Science:
- Biotechnology
- Nanomedicine
- Oncology
Background:
- Ovarian cancer presents significant treatment challenges due to late diagnosis and therapeutic resistance.
- Extracellular vesicles (EVs) show promise as drug delivery vehicles, but efficient engineering and targeting remain hurdles.
Purpose of the Study:
- To develop a scalable method for engineering extracellular vesicles (EVs) for targeted delivery to ovarian cancer.
- To create engineered EVs (eEVs) that can specifically target and track EphB4-overexpressing ovarian tumors.
Main Methods:
- Systematic screening of vesicle-anchoring domains for optimized cargo loading.
- Engineering ExpiCHO cells for large-scale production of engineered EVs (eEVs).
- Modification of a transmembrane scaffold to display Ephrin-B2 (EB2) for targeting EphB4-overexpressing ovarian cancer cells.
Main Results:
- Engineered EVs (eEVs) with bioluminescent cargo demonstrated preferential accumulation in EphB4-positive ovarian tumors in vivo.
- The Ephrin-B2 (EB2) modification enabled selective localization of eEVs to EphB4-positive xenograft tumors.
- Non-invasive tracking of eEVs and cargo distribution within tumors was achieved using bioluminescence resonance energy transfer.
Conclusions:
- A scalable and translational strategy for producing engineered EVs (eEVs) for ovarian cancer therapy was established.
- Targeted delivery of cargo to EphB4-expressing ovarian tumors using engineered EVs is feasible.
- This approach advances EV-based platforms for precision medicine in ovarian cancer treatment.
