GoKawiilThe retina is hard to penetrate with drugs because it has a protective barrier.Credit: Paul Whitten/Science Photo Library
Scientists have used pig semen to develop eye drops that can stop tumour growth in the retina and preserve vision, a study1 in mice shows. The work is published today in Science Advances.
It is hoped that the drops could be developed to treat children with retinoblastoma, a cancer of the retina. The condition is typically treated with injections of drugs into the eye, chemotherapy or laser therapy, all of which can damage non-cancerous parts of the eye. Yu Zhang and colleagues at Shenyang Pharmaceutical University in China wanted to develop a method that could penetrate the barrier around the retina and deliver the drugs without causing any unnecessary damage.
The eye drops contain exosomes — tiny particles released by almost every type of cell — engineered to carry molecules that kill cancer cells. Mice treated with the eye drops showed signs that the tumours had stopped growing. They also had comparable eyesight to control animals without tumours.
The team showed that it was possible for exosomes to penetrate the retina. The technique could improve drug delivery across other barriers that are similarly difficult to breach, such as the blood–brain barrier — to treat conditions including Alzheimer’s disease — or the mucosal barrier, says Chunxia Zhao, a researcher studying drug delivery and nanomedicine at Adelaide University in Australia.
Crossing barriers
The team used exosomes derived from semen because the particles enable sperm to penetrate the female reproductive tract. In studies with human corneal cells, the researchers determined that the exosomes from pig semen can open and close tight junctions — semipermeable structures found in the external membrane of the cells on the surface of the eye.
The researchers loaded the exosomes with a ‘nanozyme system’, containing carbon dots, manganese dioxide and glucose oxidase, to attack the cancer. When applied to the eye, the exosomes selectively penetrated tumour cells, and the nanozyme system then triggered their destruction. To improve the exosomes’ selectivity, the team attached them to folic acid molecules. Retinoblastoma cells have much higher levels of folic acid than healthy cells do.
When the researchers tested the drops in mice with retinal tumours, they observed that, 30 days later, the tumours remained small and the mice still had healthy eyesight. Among mice given eye drops containing components of the nanozyme system that were not packaged in exosomes, the tumours continued to grow — and spread to other parts of the eye — because the components could not penetrate the barrier around the eye.