byKrystal Kasal, Medical Xpress

Getting past the barrier surrounding the eye is a difficult but necessary part of treating retinoblastoma (RB)—a form of eye cancer that is more common in children. Once the barrier is penetrated, RB responds well to treatment. However, current methods, such as injections, chemotherapy, and radiotherapy, are painful and often cause vision loss and other serious side effects. But, a new method, described in a studypublishedinScience Advances, might offer a safer, more effective way to treat RB.

Penetrating the eye barrier without vision loss

Past studies have shown that tiny vesicles called exosomes, which are naturally secreted by cells, have shown promise as drug carriers due to their ability to cross biological barriers and their low immune response. Semen-derived exosomes (SEVs), in particular, have evolved to penetrate through the female reproductive tract with the help of specific proteins.

"These proteins enable SEVs to traverse formidable biological barriers, suggesting that SEVs may have inherent properties conducive to penetrating ocular barriers. This unique capability positions SEVs as a promising vehicle for noninvasive drug delivery to the posterior segment of the eye," the authors of the new study write.

To test out this theory, the team engineered eye drops that combine SEVs with folic acid (FA) and a nanozyme system (CMG) composed of carbon dots, manganese dioxide, and glucose oxidase. The CMG system triggers intense oxidative stress in tumor cells, leading to their self-destruction while sparing healthy tissue. The folic acid helps to target tumors, while the SEVs encapsulate the other components and temporarily and reversibly open tight junctions in the eye's protective layers to enter with the drug. The eye drop system as a whole is referred to as "FA-SEVs@CMG."

The SEVs were isolated from pig semen and loaded with the CMG nanozyme system. When tested, the team found that the SEVs in the eyedrops were capable of entering via two pathways: the corneal route and the conjunctival route. The researchers say this provides an "omnidirectional attack" strategy against disease.

Promising results in mice

The eye drops were tested in both cell cultures and animal models for drug delivery, tumor suppression, and safety. In vivo tests were done in mice with eye tumors. Mice treated with FA-SEVs@CMG showed significant reduction in tumor size over 30 days of eye drop treatment, compared with untreated mice and mice treated with other methods, including carbon dots (CD) and CMG without the SEV vehicle.

The FA-SEVs@CMG group showed only around 2.35% of the residual tumor mass after 30 days compared to the untreated mice. In addition, untreated mice suffered from severe neovascularization and intraocular opacity, while FA-SEVs@CMG– and SEVs@CMG–treated mice maintained near physiological clarity at 30 days of treatment.

The study authors write, "This groundbreaking study on SEVs marks a paradigm shift in posterior ocular disease therapeutics. Unlike existing delivery methods such as microparticles or microneedles, the SEV-based eye drop platform avoids potential ocular structural damage and systemic toxicity. Critically, whereas conventional microparticles or microneedles exhibit unidirectional diffusion within the eye, the dual-pathway delivery via both corneal and conjunctival routes with SEV eye drops offers distinct advantages for the noninvasive treatment of fundus diseases, such as ocular fundus tumors."

Despite the unconventional origins of the newly developed eye drops, the new methods offer hope for safer, more effective, and less invasive treatments for childhood eye cancer. The team also notes that the method may be useful for other ocular diseases, such as age-related macular degeneration or diabetic retinopathy. Further research and development is required before human trials can take place, as the team says that large-scale production and clinical translation for SEVs still face challenges, including controlling batch-to-batch variation, meeting manufacturing standards, mitigating immunogenicity, and addressing pathogen contamination risks.

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Publication details Jiansong Zhao et al, Harnessing semen-derived exosomes for noninvasive fundus drug delivery: A paradigm for exosome-based ocular fundus therapeutics, Science Advances (2026). DOI: 10.1126/sciadv.adw7275 Journal information: Science Advances