The swimmers seem to be a good drug delivery system.
We know sperm as the little swimmers that can get women pregnant, but researchers are testing out a novel use for them: They could also help treat cervical cancer and other gynecologic diseases, according to a study published this month in ACS Nano.
Treatments like chemotherapy and radiation come with a host of side effects like nausea, vomiting, and hair loss. That’s because the drugs attack both rogue cancer cells and healthy ones. To minimize complications, researchers have been experimenting with targeted drug delivery systems that send cancer-killing drugs directly to the diseased cells. But this is the first time they’ve given it a spin with sperm.
For the study, researchers from the Leibniz Institute for Solid State and Materials Research in Dresden, Germany, transformed bovine sperm into tiny torpedos and set them loose on a tumor-like mass in a petri dish. First, they doused 3,500 sperm in doxorubicin hydrochloride, a common anticancer drug that sperm can absorb into their membranes, says study author Mariana Medina-Sánchez, a researcher at the institute. Ninety-eight percent of the sperm soaked up the drug, mostly in the cytoplasm and nucleus in their heads.
Then Medina-Sánchez and her team used nanotechnology to fit the sperm with 3D-printed suits of armor made out of titanium and iron. Each of these “micromotors” consists of a microscopic tube and four bendable arms that act as a gate to keep the sperm (and the drugs) in place until it’s time to attack, like this:
Then they used weak magnetic fields to guide the suited-up sperm to a mass made of HeLa cells, an immortal cell line that a scientist from Johns Hopkins Hospital derived from a woman’s cervical cancer tissue in 1951. (Her name was Henrietta Lacks, hence “HeLa” cells. Yes, the woman Oprah played in a movie earlier this year.)
The attack officially began when the sperm collided with the tumor-like mass. The four arms on the spermbot suits opened and released the drug-soaked swimmers straight into the tumor. Over the next 72 hours, these sperm killed 87 percent of the cancer cells. In a separate petri dish, a similar tumor-like mass sat in a solution containing the same amount of the drug; that solution killed only 55 percent of the cells over the same period. The spermbots delivered the drug directly into the cells while the solution only reached their outer layer, the researchers report.
Sperm’s potential as a treatment method for cervical cancer (which is caused by HPV) and other gynecologic diseases comes down to a few key characteristics, Medina-Sánchez says. For one, the strong swimmers are built to survive in the female genital tract. “Their swimming ability allows them to penetrate the tumor tissue, releasing the drug not only in the tumor’s surroundings but into its interior cells,” she explains.
And just like sperm can fuse with eggs in the fallopian tubes, they can fuse with non-reproductive cells, too. “This means they can fuse with cancer cells and deliver the drug inside them,” she says. The sperm also absorb the drugs and keep bodily fluids from diluting the drugs’ concentration, a common challenge in this line of work, the authors write.
Plus, sperm are virtually immune to the drug they tested. Doxorubicin hydrochloride kills cancer cells by preventing DNA replication and protein synthesis, which make it more difficult for the cancer cells to survive. But since sperm already have short lifetimes and they don't replicate, they're protected from the drug’s effects, Medina-Sánchez says.
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She and her team still have lots to work out before testing this technology in women. They hope to increase the drug dose and test it in cultures with cancerous and healthy cells to see how well the spermbots target and kill just the cancerous ones, she says. And even though the magnetic fields are weak, they want to avoid leaving behind thousands of metal magnets in women’s bodies by making the sperm’s magnetic suit completely biodegradable. Finally, they used bovine sperm in the study, but Medina-Sánchez says men could presumably donate their sperm for the treatments.
But, uh, what about the sperm’s baby-making skills? Women can get pregnant when sperm wiggle their way through the cervix, past the uterus, and into the fallopian tubes where they can fertilize eggs. So could women accidentally get pregnant from this treatment?
“The goal is to use viable, healthy sperm and the primary point of healthy sperm is to find the egg and impregnate,” says Bradley Corr, a practicing OB/GYN and an assistant professor of gynecologic oncology at the University of Colorado Denver, who was not involved in the study. “I do think it would be possible for a patient to get pregnant with this delivery system, but I think there are ways around that.” For example, doctors could suppress women’s hormones to prevent ovulation much like hormonal contraceptives do, he says. (Meaning there would be no eggs released for said sperm to fertilize.)
He and Medina-Sánchez agree that pregnancy would be unlikely since doctors would guide the spermbots to the tumors—not to the eggs. If it did somehow fuse with an egg, the spermbot would inject it with cancer drugs. That’s...not great. “Obviously this has never been studied before, so the outcomes would truly be unknown,” Corr says. But in theory, the drugs could lead to miscarriage or cause issues with the neonatal fetus, or they could prevent the egg from developing into a viable pregnancy altogether.
Corr points out that spermbots might help scientists develop other effective ways to deliver drugs rather than become a mainstream treatment themselves. “Drug delivery systems are a hot topic of investigation in cancer care right now, specifically the use of nanoparticles and how to better deliver drugs to the appropriate cells,” he says. “I think this study would more likely lead to further development of better nanoparticle drug delivery systems rather than be used as this specific delivery system.”
This study marks another advancement in cancer care research, whether it becomes a mainstream treatment or not. “Bio-hybrid delivery systems are promising because they combine the advantages of the biological components like cells and microorganisms with the properties of man-made micro- and nanostructures,” Medina-Sánchez says. The man-made structures make it possible to guide the cells and microorganisms to diseased areas with things like magnetic fields, ultrasound, and light, she adds.
“We’re currently taking our first steps towards smarter, active drug delivery systems using all the advantages that sperm cells offer us, which we’re sure will be of great benefit for different biomedical applications in the future,” she says. “We believe that after solving some of the most urgent limitations, the [sperm-hybrid] system could be successfully used to treat diseases in the female reproductive tract.”
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