Human Spermbots for Cancer-Relevant Drug Delivery

Abstract: Cellular micromotors are attractive for locally delivering high concentrations of drug and targeting hard-to-reach disease sites such as cervical cancer and early ovarian cancer lesions by non-invasive means. Spermatozoa are highly efficient micromotors perfectly adapted to traveling up the female reproductive system. Indeed, bovine sperm-based micromotors have recently been reported as a potential candidate for the drug delivery toward gynecological cancers of clinical unmet need. However, due to major differences in the molecular make-up of bovine and human sperm, a key translational bottleneck for bringing this technology closer to the clinic is to transfer this concept to human sperm. Here, we successfully load human sperm with a chemotherapeutic drug and perform treatment of relevant 3D cervical cancer and patient-representative 3D ovarian cancer cell cultures, resulting in strong anti-cancer effects. Additionally, we show the subcellular localization of the chemotherapeutic drug within human sperm heads and assess drug effects on sperm motility and viability over time. Finally, we demonstrate guidance and release of human drug-loaded sperm onto cancer cell cultures by using streamlined microcap designs capable of simultaneously carrying multiple human sperm towards controlled drug dosing by transporting known numbers of sperm loaded with defined amounts of chemotherapeutic drug.