Three-Dimensional Tumor Spheroid Model as a Tool to Optimize the Nano-Bio Interface
K Bromma1*, W Beckham2, D Chithrani1,2, (1) University of Victoria, Victoria, BC, CA, (2) BC Cancer - Vancouver Island Centre, Victoria, BC, CA
Presentations
TH-C-TRACK 6-6 (Thursday, 7/29/2021) 1:00 PM - 2:00 PM [Eastern Time (GMT-4)]
Purpose: Radiotherapy and chemotherapy are the gold standard for treating patients with cancer in the clinic, which 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 tumor spheroid models that can better approximate the tumor environment compared to a two-dimensional monolayer model have been used.
Methods: 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, which can act as a radiosensitizer, was also utilized, informing future potential of gold nanoparticle-mediated combined therapeutics. The optimal treatment dose was elucidated using a resazurin-based proliferation assay. The uptake of GNPs into the cells was measured using inductively-coupled plasma mass spectrometry and imaged using darkfield microscopy.
Results: In the 2D monolayer model, the addition of docetaxel induced a small, non-significant increase of uptake of gold nanoparticles of between 13% and 24%. In the 3D spheroid model, docetaxel increased uptake by between 47% and 186%, with CAL-27 having a larger increase relative to HeLa. Further, the depth of penetration of 15 nm gold nanoparticles over 50 nm gold nanoparticles increased by 33% for CAL-27 spheroids and 17% for HeLa spheroids.
Conclusion: These results highlight the necessity to optimize gold nanoparticle 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. Inclusion of a more complex model into future lab experiments is imperative for future clinical translation.
Funding Support, Disclosures, and Conflict of Interest: This work was funded by the Natural Sciences and Engineering Research Council of Canada.
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