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    Human spermbots for patient-representative 3D ovarian cancer cell treatment

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    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.
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    Affiliation
    Institute for Integrative Nanosciences, Leibniz IFW Dresden, Helmholtzstraße 20, 01069 Dresden, Germany.
    Issue Date
    2020
    
    Metadata
    Show full item record
    Abstract
    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
    Nanoscale
    URI
    http://hdl.handle.net/10541/623453
    DOI
    10.1039/d0nr04488a
    PubMed ID
    33026016
    Additional Links
    https://dx.doi.org/10.1039/d0nr04488a
    Type
    Article
    ae974a485f413a2113503eed53cd6c53
    10.1039/d0nr04488a
    Scopus Count
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    All Paterson Institute for Cancer Research

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