Speaker
Description
Radiotherapy 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. The radiosensitization effects on monolayer vs spheroids with the different sized GNPs was also elucidated. In the 2D monolayer model, the addition of DTX induced a small, non-significant increase of uptake of GNPs of approximately 20% while in the 3D spheroid model, DTX increased uptake by between 50% and 200%, 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 for both cancer spheroids. Measurement of the responses to radiation with GNPs yielded a large radiosensitization effect, with more of the cells on the periphery of the spheroid being affected. 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 and the introduction of an extracellular matrix, which are absent from a simple 2D monolayer model.
