Three-dimensional Tumor Spheroids as a Tool for Reliable Investigation of Combined Gold Nanoparticle and Docetaxel Treatment

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dc.contributor.authorBromma, Kyle
dc.contributor.authorAlhussan, Abdulaziz
dc.contributor.authorPerez, Monica Mesa
dc.contributor.authorHoward, Perry
dc.contributor.authorBeckham, Wayne
dc.contributor.authorChithrani, Devika B.
dc.date.accessioned2021-04-03T15:17:25Z
dc.date.available2021-04-03T15:17:25Z
dc.date.copyright2021en_US
dc.date.issued2021
dc.description.abstractRadiotherapy and chemotherapy are the gold standard for treating patients with cancer in the clinic but, despite modern advances, are limited by normal tissue toxicity. The use of nanomaterials, such as gold nanoparticles (GNPs), to improve radiosensitivity and act as drug delivery systems can mitigate toxicity while increasing deposited tumor dose. To expedite a quicker clinical translation, three-dimensional (3D) tumor spheroid models that can better approximate the tumor environment compared to a two-dimensional (2D) monolayer model have been used. We tested the uptake of 15 nm GNPs and 50 nm GNPs on a monolayer and on spheroids of two cancer cell lines, CAL-27 and HeLa, to evaluate the differences between a 2D and 3D model in similar conditions. The anticancer drug docetaxel (DTX) which can act as a radiosensitizer, was also utilized, informing future potential of GNP-mediated combined therapeutics. In the 2D monolayer model, the addition of DTX induced a small, non-significant increase of uptake of GNPs of between 13% and 24%, while in the 3D spheroid model, DTX increased uptake by between 47% and 186%, with CAL-27 having a much larger increase relative to HeLa. Further, the depth of penetration of 15 nm GNPs over 50 nm GNPs increased by 33% for CAL-27 spheroids and 17% for HeLa spheroids. These results highlight the necessity to optimize GNP treatment conditions in a more realistic tumor-life environment. A 3D spheroid model can capture important details, such as different packing densities from different cancer cell lines, which are absent from a simple 2D monolayer model.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipThis study was funded by NSERC Discovery Grant.en_US
dc.identifier.citationBromma, K., Alhussan, A., Mesa Perez, M., Howard, P., Beckham, W., & Chithrani, D. B. (2021). Three-Dimensional Tumor Spheroids as a Tool for Reliable Investigation of Combined Gold Nanoparticle and Docetaxel Treatment. Cancers, 13(6), 1-19. https://doi.org/10.3390/cancers13061465.en_US
dc.identifier.urihttps://doi.org/10.3390/cancers13061465
dc.identifier.urihttp://hdl.handle.net/1828/12830
dc.language.isoenen_US
dc.publisherCancersen_US
dc.subjectgold nanoparticles
dc.subjectmulticellular spheroids
dc.subjectmonolayer
dc.subjectdocetaxel
dc.subjectuptake
dc.subjectcell nanomedicine
dc.subjectCentre for Advanced Materials and Related Technology (CAMTEC)
dc.subjectCentre for Biomedical Research
dc.subject.departmentDepartment of Physics and Astronomy
dc.subject.departmentDepartment of Biochemistry and Microbiology
dc.subject.departmentDepartment of Biology
dc.subject.departmentSchool of Medical Sciences
dc.titleThree-dimensional Tumor Spheroids as a Tool for Reliable Investigation of Combined Gold Nanoparticle and Docetaxel Treatmenten_US
dc.typeArticleen_US

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