Human spermbots for patient-representative 3D ovarian cancer cell treatment
Authors
Xu, H.Medina-Sánchez, M.
Zhang, W.
Seaton, Melanie
Brison, D. R.
Edmondson, R. J.
Taylor, Stephen S
Nelson, Louisa
Zeng, K.
Bagley, Steven
Ribeiro, C.
Restrepo, L. P.
Lucena, E.
Schmidt, Christine K
Schmidt, O. G.
Affiliation
Institute for Integrative Nanosciences, Leibniz IFW Dresden, Helmholtzstraße 20, 01069 Dresden, Germany.Issue Date
2020
Metadata
Show full item recordAbstract
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 shown potential to carry drugs toward gynecological cancers. 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 material. Here, we successfully load human sperm with Doxorubicin (DOX) and perform treatment of 3D cervical cancer and patient-representative ovarian cancer cell cultures, resulting in strong anticancer cell effects. Additionally, we define the subcellular localization of the chemotherapeutic drug within human sperm, using high-resolution optical microscopy. We also assess drug effects on sperm motility and viability over time, employing sperm samples from healthy donors as well as assisted reproduction patients. Finally, we demonstrate guidance and release of human drug-loaded sperm onto cancer tissues using magnetic microcaps, and show the sperm microcap loaded with a second anticancer drug, camptothecin (CPT), which unlike DOX is not suitable for directly loading into sperm due to its hydrophobic nature. This co-drug delivery approach opens up novel targeted combinatorial drug therapies for future applications.Citation
Xu H, Medina-Sanchez M, Zhang W, Seaton MPH, Brison DR, Edmondson RJ, et al. Human spermbots for patient-representative 3D ovarian cancer cell treatment. Nanoscale. 2020;12(39):20467-81.Journal
NanoscaleDOI
10.1039/d0nr04488aPubMed ID
33026016Additional Links
https://dx.doi.org/10.1039/d0nr04488aType
Articleae974a485f413a2113503eed53cd6c53
10.1039/d0nr04488a
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