  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.
