Ferritin-Nanocaged ATP Traverses the Blood–Testis Barrier and Enhances Sperm Motility in an Asthenozoospermia Model

Sperm motility can be enhanced by adding ATP exogenously during in vitro fertilization. However, administering exogenous ATP to the testis to improve sperm motility for in vivo asthenozoospermia treatment has not been investigated yet. Inspired by the recent advances in nanomedicine, we investigated whether the capability of drug delivery nanocarriers to traverse the blood–testis barrier (BTB) can facilitate ATP-dependent asthenozoospermia treatment. We found that the human H-ferritin (HFn) nanocarrier possesses the capability to traverse the BTB and specifically targets the head of elongated sperm cells. Specifically, the HFn nanocarrier traversed the BTB and accumulated in the sperm heads by binding with the HFn receptor (HFR), whose expression was relatively low in Sertoli cells but high in sperm heads. In a gossypol-induced mouse asthenozoospermia model, the administration of an ATP-loaded HFn nanocage through a tail vein injection significantly improved sperm motility. Moreover, the HFn nanocarrier was not toxic to mice in the short (1d) and long terms (30d, 90d) nor did it affect their reproductive health. Thus, the ATP-loaded HFn nanocarrier can potentially serve as a drug-delivery system for treating asthenozoospermia.