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Ovarian cancer is difficult to treat, in part because it is often diagnosed late and tumors can vary widely between patients. Delivering therapies directly to cancer cells while avoiding healthy tissue remains a major challenge in oncology.
Researchers at The University of Queensland have developed a new strategy to engineer extracellular vesicles for more effective and targeted drug delivery. Extracellular vesicles are small, naturally occurring particles released by cells that can carry molecular cargo such as proteins or RNA.
The team focused on improving both how these vesicles are produced and how they deliver their cargo. They identified optimal molecular “anchors” that help package therapeutic molecules into vesicles more efficiently. They also used engineered cells, specifically ExpiCHO cells, to create a scalable system for producing large amounts of these vesicles.
Engineering extracellular vesicles for targeted delivery in ovarian cancer
EV cargo loading was optimized by comparing vesicle-anchoring domains to enhance reporter protein packaging. The selected strategy was applied to scalable production using mammalian cell systems, followed by the generation of stable engineered cell lines for consistent EV yield. Engineered EVs were then evaluated in ovarian cancer PDX models to assess in vivo biodistribution and tumor targeting.
To guide the vesicles to tumors, the researchers modified their surface with a targeting molecule called Ephrin-B2. This molecule binds to a receptor called EphB4, which is commonly found at high levels in ovarian cancer cells. This targeting strategy allows the engineered vesicles to selectively accumulate in tumor tissue after being introduced into the body.
The researchers tested their system in advanced models of ovarian cancer and showed that the vesicles could successfully deliver their cargo to tumors. They also incorporated a bioluminescent signal into the cargo, allowing them to track where the vesicles travel and how effectively they deliver their payload.
This approach demonstrates a promising way to use extracellular vesicles as targeted delivery vehicles in cancer treatment. By combining scalable production with precise targeting, the method could support the development of more personalized and effective therapies for ovarian cancer and potentially other diseases.
