Mike Mcrae, in a must read piece in Science Alert, reports on “spermbots” wearing a “iron suit” that will guide them via magnetic fields to deliver toxic drugs to kill the cells of a woman’s reproductive system that are affected by cancer.
He highlights the work of researchers from the Institute for Integrative Nanosciences and the Chemnitz University of Technology in Germany, who have discovered “a way to harness a process already well adapted to navigating the harsh environments of the vagina, cervix, uterus, and fallopian tubes to treat conditions such as gynecological cancer, endometriosis, and pelvic inflammatory diseases.”
Delivering drugs in effective doses to the right site without damaging healthy cells is one of the main challenges in research on cancer treatment.
Packing the drugs in tiny bubbles, such as in microscopic vessels called liposomes, helps make them more soluble and helps protect the body from the toxic contents as they're carried through the body.
Unfortunately there are still a bunch of other problems to solve, including dilution of the packages as they spread through the body and getting the drug inside the target cells.
Nature does offer a solution in the form of cells that can propel themselves in a specific direction thanks to a 'motorised' whip called a flagellum, while sniffing out chemical hotspots to zero in on.
Thanks to this, many species of bacteria would be perfectly suited to navigating pathways through the body either in search of a chemically labelled beacon or under some sort of external control, if not for the unfortunate fact that they'd probably be gobbled up by our immune system long before they succeeded in their mission.
McRae notes that sperm is the perfect weapon in navigating and delivering the medicine within a woman’s reproductive tract as their membrane offers a “perfect way to package drugs to avoid dilution, immune responses, or break-down from the body's enzymes”. As sperm fuses with the ova during fertilization they can deliver drugs directly into cells.
From the researchers conclusion:
We have proposed a novel drug delivery system based on sperm-hybrid micromotors. In such assembly, sperms are utilized as drug carriers for potential cancer treatment in the female reproductive tract, as the sperm membrane can penetrate cancer cells thanks to its capacity to fuse with somatic cells,56 efficiently transferring the drug to the target cell/model tumor in the process. Moreover, the sperm cells serve as propulsion source while the magnetic microstructure is used for guidance and release of the sperm: When the arms of the microstructure hit Hela cells, they bend and thus open a way to free the sperm.
Bovine sperms were used as model cells to load DOX HCl drug for treatment of cervical cancer. For that, HeLa cell spheroids were cultured as an in vitro tumor model. DOX-HCl was locally distributed into the HeLa cell clusters after the sperm cells were released, showing higher tumor cell-killing efficacy within the first 48h, compared to the drug solution with the same dose.
Sperms also showed surprisingly high drug encapsulation capacity compared to liposomes or other synthetic carriers. Furthermore, the sperm was capable to swim through complex environments in an efficient manner not only due to their tail beating but also due to their membrane biochemistry. A set of enzymes is expressed by sperms to catalyze 21the degradation of hyaluronic acid, which contributes to the constitution of the extracellular matrix of oocyte-surrounding cumulus cells.57 It was widely reported that hyaluronic acid also plays an important role in the proliferation and migration of tumor tissue.58 Therefore the motility and the hyaluronidases wielded by sperm cells allow them to penetrate deep into a tumor spheroid for effective in situ drug administration. Besides, sperm cells can remain functional in the human body for a longer time in comparison to other foreign cells due to the ability to inhibit the immune response by displaying specific glycans on the membrane.59 This reduces undesired immune response and thus makes this system compatible to the host body. Such sperm-hybrid micromotors not only have potential application for gynecologic cancer treatment but also for treating other diseases in the female reproductive tract such as endometriosis, pelvic inflammatory diseases, among others. Such devices can be also engineered to carry genes, mRNA, imaging contrast agents, among other substances of interest for diverse biomedical applications. Furthermore, these self-propelled carriers are promising to avoid the dilution in body fluids and undesired accumulation of such cargo, in contrast to other conventional carriers, as the cargo is internalized by the sperm and protected by its membrane. This drug loading process does not seem to interfere with sperm motility due to the sperm cell's incomplete metabolism that avoids intracellular degradation of the drug.
Although there are still some challenges to overcome before this system can be applied in in vivo environments (e.g. imaging, biodegradation of the synthetic part, multiple sperms carrying and delivery, and improved control of sperm release), sperm-hybrid systems may be envisioned to be applied in in situ cancer diagnosis and treatment in the near future.
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