Scientists at the UF Health Cancer Institute have developed a novel drug-delivery strategy that could significantly improve treatment for triple-negative breast cancer, one of the most aggressive and difficult-to-treat forms of the disease.
In a study published in the Journal of Extracellular Vesicles, the research team demonstrated that extracellular vesicles — tiny lipid-based particles naturally released by cells — can be used to safely and efficiently transport powerful anti-cancer drugs directly to tumors. The approach overcomes two major barriers that have long limited the effectiveness of advanced targeted therapies: poor tumor penetration and drug instability in the bloodstream.
The researchers focused on proteolysis-targeting chimaeras, or PROTACs, a new class of drugs designed to eliminate cancer-promoting proteins by hijacking the cell’s natural protein-disposal system. While PROTACs have shown strong tumor-killing potential in laboratory experiments, they have struggled to perform in living organisms because they break down easily and have difficulty reaching tumor sites.
To solve this, the UF team packaged PROTACs inside extracellular vesicles, creating a protective carrier that could escort the drugs through the body and deliver them more precisely to cancer cells. In mouse models of triple-negative breast cancer, this EV-based delivery system led to significantly reduced tumor growth and longer survival compared with PROTACs delivered on their own.
“We wanted to see if extracellular vesicles might overcome these challenges of poor delivery and instability of this targeted drug,” said Nina Erwin, a doctoral candidate in pharmaceutics at the UF College of Pharmacy and lead author of the study.
Using a newly developed loading technique, the researchers infused extracellular vesicles with a form of PROTACs designed to suppress tumor growth without damaging healthy cells. The method improved how much drug could be packed into each vesicle and preserved the drug’s activity as it traveled through the body.
The result was a therapy that not only reached tumors more efficiently, but also maintained its potency long enough to attack them once it arrived.
“I think this proof-of-concept study opens a door to using extracellular vesicles as a delivery platform technology,” Erwin said. “It’s not limited to one type of drug or even to one type of cancer. It could help move effective but hard-to-deliver drugs closer to clinical use.”
Triple-negative breast cancer accounts for about 10 to 15 percent of breast cancer cases and is known for its rapid growth, early spread and high risk of recurrence. Its tumors vary widely in their molecular characteristics, making them particularly resistant to conventional targeted treatments.
By improving drug stability and bioavailability, the extracellular-vesicle approach could provide a much-needed breakthrough for this difficult-to-treat cancer, said Mei He, Ph.D., an associate professor in the UF College of Pharmacy and senior author of the paper.
“Solving this delivery issue could allow for a quicker clinical translation for other similar drugs,” He said.
The study was the result of a multidisciplinary collaboration involving researchers from the UF College of Pharmacy, the UF College of Medicine and UF’s Department of Medicinal Chemistry. In addition to Erwin and He, the team included Guangrong Zheng, Ph.D.; Daiqing Liao, Ph.D.; and Weizhou Zhang, Ph.D.
Researchers believe the findings represent a meaningful step toward turning promising laboratory drugs into viable therapies for patients — and may pave the way for using extracellular vesicles as a universal platform for delivering next-generation cancer treatments.
