Using Magnetism to Direct Drug Carrying Sperm to Cancerous Tumors
Current means of drug delivery can be highly effective, but also come with a multitude of downfalls. Some of these challenges include non-specific drug uptake, reduced tissue penetration, decreased drug concentration, and high immunogenicity. To circumvent these issues, researchers have come up with a novel idea of packaging the cancer drug Doxorubicin Hydrochloride (DOX-HCL) into bovine sperm in order to effectively target cervical tumors. In order to accomplish this, DOX-HCL was successfully packaged into bovine sperm cells via ATP mediated permeabilization. The DOX-HCL packaging sperm were then characterized and compared with non DOX-HCL containing sperm. The analysis revealed that the encapsulation of DOX-HCL had no effect on sperm viability, motility, or encapsulation efficiency. After determining that DOX encapsulation had no negative side effects on the bovine sperm, the researchers analyzed the potential drug delivery ability of this system. The encapsulated sperm was incubated with spheroid HeLa cells for 72 hours before fluorescent microscopy revealed that a significant amount of DOX-HCL was not only successfully transmitted into the HeLa cells but also initiated cellular death. However, this analysis was carried out in an entirely in vitro system, therefore the authors had to identify a means of directing the drug delivering sperms to their specific tumor target once inside of the body. To resolve this issue, they decided to generate magnetic tetrapod harnesses from a 3D printer and mount them onto the heads of the drug carrying sperm. The sperm were then hyper activated via progesterone in order to ensure that they could maintain a high swimming velocity despite carrying the extra weight of the tetrapod. The sperm-tetrapod hybrids were analyzed in a more in vivo based setting by releasing them into a polydimethylsiloxane channel and guiding them to a HeLa cell spheroid using an external magnetic field. Once the tetrapods made contact with the outer layer of the spheroid, their arms bent enough to release the sperm directly onto the tumor. The sperm were then able to inject the DOX-HCL drug directly into the spheroid cells and initiate cancerous cell death. This novel means of targeted drug delivery has given researchers hope that some day soon they will able to encapsulate sperm with multitudes of cancer drugs and deliver them directly to various types of gynecological based tumors.
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