Pig semen molecule could deliver chemotherapy to hard-to-reach eye cancer, mouse study suggests

Scientists have found a way to get treatment for a rare type of cancer into the back of the eye without damaging the nearby structures: by using a molecule derived from pig semen.

The approach, which was tested in mice, targets a cancer called retinoblastoma and takes advantage of sperm’s ability to penetrate barriers. If the new technique can be demonstrated as safe and effective in people, it could help retinoblastoma patients, who are mostly young children, receive chemotherapy without having to face painful and potentially eye-damaging injections.

“Given that the majority of affected patients are young children, eye-preserving and toxicity-minimizing therapies are critically important for their lifelong well-being,” said study co-author Yu Zhang, a pharmaceutics researcher at Shenyang Pharmaceutical University in China.

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Retinoblastoma affects 1 in 18,000 children. Almost all are under 5 years old, and two-thirds are younger than 2. In retinoblastoma, the tumor is at the very back of the eye. For a drug treatment to get there, it needs to pass through either the cornea — the protective layer at the front of the eye — or the side of the eyeball. Chemotherapy for this condition is usually injected, but this can damage the eye.

To get around this problem, Zhang’s team wanted to design a safer, painless way to deliver chemotherapy to the retina. They considered what natural biological systems were particularly good at getting material across barriers and found inspiration in sperm exosomes.

Exosomes are tiny fat bubbles that cells use to send proteins or other materials from a cell’s interior to its outer membrane. In semen, exosomes are carried in the seminal fluid and ferry proteins that help the sperm cell pass through the protective layer of cells around the egg to fertilize it. Even though the cells in the eye are very different, the mechanics of passing this biological barrier appeared similar to Zhang’s team. “This led us to explore whether semen-derived exosomes also possess the ability to penetrate ocular barriers,” Zhang told Live Science.

They tested this with pig semen, because pigs are already widely used in biology research and material from pigs is generally safe to use in clinical research. Zhang’s team gave mice eye drops with pig seminal extracellular vesicles (SEVs), or exosomes, and showed that they could deliver a potential retinoblastoma treatment to the back of the eye.

This proof-of-concept delivery system was used to ferry carbon dots, or nanostructures made of carbon atoms, to the back of the mouse eye. Carbon dots are not routinely used in cancer treatment yet, but other researchers have studied how these tiny structures could be used to kill tumor cells by producing high levels of “reactive oxygen species,” which destroy the cells’ DNA. To ensure that the exosomes targeted tumor cells and not healthy eye cells, their lipid layer included additional molecules that ramped up reactive-oxygen-species production in the presence of hydrogen peroxide, which cancer cells crank out at high levels to grow and spread.

In the new study, which was published March 27 in the journal Science Advances, Zhang and colleagues showed that the eye drops permeated the layers of the mouse eye to kill tumor cells. After 30 days, the tumors were only 2-3% of the size of those in untreated mice.

This work provides some interesting insights into the application of this technique, Owen Davies, an expert in extracellular vesicles at Loughborough University in the U.K., told Live Science in an email. But he noted that other types of exosomes, such as those derived from stem cells, might work as well.

Zhang, for his part, thinks exosomes could be used to deliver other treatments for eye conditions beyond retinoblastoma, such as macular degeneration.

Dr. Shiri Zayit-Soudry, an ophthalmologist at the Rabin Medical Center of Tel Aviv University who was not involved in the study, agreed, saying in an email that the new technique “holds genuine transformative potential.” However, she cautioned that this would still require extensive testing to show if it can be used to treat other diseases and any potential applications would have to go through human clinical trials.