Yes, you read that correctly, researchers from the lab of Oliver G. Schmidt (IFW Dresden, Germany) have developed a half-biological, half-mechanical cancer-killing cyborg based on the humble spermatozoa. Specifically, the extremely virile research team loaded sperm with a cargo of chemotherapeutic drugs and provided each wriggler with a specially designed metallic harness to allow magnetic guidance and effective sperm release when the cyborg encounters a cancerous cell.
“But why?!” I hear you ask. Advanced drug delivery systems aim to provide controlled and localized doses of drugs while also aiming to limit non-specific delivery, improve tissue penetration, and decrease applied dosages. The team had already adapted cyborg sperm technology for in vivo assisted fertilization (Magdanz et al and Medina-Sánchez et al) and Xu et al saw further potential for sperm as an effective and efficient drug delivery system for the targeted treatment of gynecological cancer.
- So why choose sperm over other systems?
- Sperm are readily available, naturally motile, and environmentally adapted to the female reproductive system
- Lack of pathogenicity or proliferation makes sperm safer than other motile cells (e.g. bacteria) or tumor-tropic cells (e.g. human stem cells), which are other interesting drug delivery systems
- Lack of immunogenicity enables long-term sperm survival and therefore, better drug availability
- Sperm can stably carry high cargo loads, as certain characteristics of the sperm nucleus allows the encapsulation and protection of high concentrations of hydrophilic drugs (This minimizes toxic side-effects in healthy tissues and degradation of the cargo while “in transit”)
- Sperm can also fuse with cell membranes (normally ova) to effectively deliver a cargo.
- For these reasons, the authors loaded cow sperm (a model for human sperm) with a potent cervical cancer chemotherapeutic drug (doxorubicin)
- Using two-photon 3D nanolithography, the authors then “printed” a four-armed tubular microstructure that surrounds each sperm.
- The arms mediate the in situ mechanical release of the drug-loaded sperm cell after encountering a cancer cell and promote sperm-cancer cell fusion to specifically release drugs into the cancer cell cytoplasm
- The sperm tail itself provides self-propulsion, while an external magnetic field can guide the metal jacket to the target site
- The results?
- When tested against a HeLa cell tumor cluster (gynecological cancer model) the team efficiently targeted sperm and discharged doxorubicin into the cancer cells
- Excitingly, the cyborg sperm displayed a higher tumor cell-killing efficacy compared to a similar dose of free drug solution
Suddenly the future doesn’t seem so far away. But wait, there’s more! The team also suggests that their advanced drug delivery system could be adapted to treat other diseases of the female reproductive tract (e.g. endometriosis and pelvic inflammatory diseases) and engineered to carry other relevant cargos (e.g., genes, mRNA, or imaging contrast agents).
To see how cyborg sperm could be wriggling their way to success, head over to arXiv now!