Our paper titled "Blood-testis barrier-crossing extracellular vesicles for asthenospermia therapy via synergistic ATP replenishment and ferroptosis suppression" has been accepted by the journal Biomaterials.
Nanotherapy Crosses the Blood-Testis Barrier, Offering New Hope for Male Infertility Treatment
A new study published in the prestigious journal Biomaterials unveils a promising non-invasive strategy for treating asthenozoospermia, a major cause of male infertility characterized by reduced sperm motility. The research team has developed engineered therapeutic nanoparticles that can successfully cross the highly restrictive blood-testis barrier (BTB)—a longstanding challenge in male reproductive medicine.
The study, titled "Blood-testis barrier-crossing extracellular vesicles for asthenozoospermia therapy via synergistic ATP replenishment and ferroptosis suppression," engineers tiny biological carriers, known as extracellular vesicles (EVs), to deliver energy-boosting adenosine triphosphate (ATP) directly to sperm-producing cells while simultaneously inhibiting a specific form of cell death called ferroptosis.
"This platform is a significant leap forward because it directly addresses two root causes of asthenozoospermia—energy depletion and oxidative cell damage—while solving the fundamental problem of drug delivery to the testes," said the senior author of the study. "We've essentially created a targeted delivery system that seeks out and repairs the damaged environment where sperm are created."
Overcoming the Biological Fortress
The blood-testis barrier protects developing sperm from toxins and the immune system but also blocks most therapeutic drugs. To overcome this, researchers derived EVs from human umbilical cord mesenchymal stem cells (UCMSCs), which possess a natural ability to traverse biological barriers. These EVs were loaded with ATP and functionalized with a special fluorescent dye (an AIEgen) that glows in the near-infrared-II (NIR-II) window, allowing researchers to track their journey in real-time using advanced imaging.
The results were clear: following injection, the engineered EVs efficiently crossed the BTB and accumulated within the seminiferous tubules of the testes, the site of sperm production.
A Dual-Action Therapeutic Strategy
Once inside the testicular environment, the EVs perform a dual therapeutic function:
ATP Replenishment: The released ATP directly fuels spermatogenic cells, restoring their energy levels and significantly improving sperm motility.
Ferroptosis Suppression: The EVs themselves upregulate a key antioxidant enzyme, glutathione peroxidase 4 (GPX4), which combats ferroptosis—an iron-dependent form of cell death recently implicated in sperm dysfunction.
In mouse models of busulfan-induced asthenozoospermia, treatment with the EVs@ATP platform led to remarkable recovery. Sperm count, motility, and swimming velocity (kinematic parameters) showed significant improvement. Furthermore, the therapy restored healthy testicular structure and demonstrated no signs of systemic toxicity, confirming its safety.
A Promising Path to the Clinic
This research presents a multifunctional nanoplatform that mergers precise imaging with targeted, synergistic therapy. By non-invasively delivering a combined treatment for energy deficiency and oxidative stress directly to its site of action, this strategy offers a powerful and promising new avenue for treating male infertility.
"The ability to visually confirm that our therapy reaches its target, and then see such a robust restoration of sperm function, is incredibly encouraging," added a lead researcher. "We believe this approach holds tremendous potential for future clinical translation."
About the Journal
Biomaterials is a leading international journal covering the science and application of biomaterials and associated medical devices.
https://www.sciencedirect.com/science/article/pii/S0142961225006969