Bromma Kyle, Alhussan Abdulaziz, Perez Monica Mesa, Howard Perry, Beckham Wayne, Chithrani Devika B
Department of Physics and Astronomy, University of Victoria, Victoria, BC V8P 5C2, Canada.
Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8P 5C2, Canada.
Cancers (Basel). 2021 Mar 23;13(6):1465. doi: 10.3390/cancers13061465.
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. 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.
放射疗法和化学疗法是临床上治疗癌症患者的金标准，但尽管有现代进展，仍受正常组织毒性的限制。使用纳米材料，如金纳米颗粒（GNP），来提高放射敏感性并作为药物递送系统，可以减轻毒性，同时增加肿瘤沉积剂量。为了加快临床转化速度，已经使用了三维（3D）肿瘤球体模型，与二维（2D）单层模型相比，该模型能更好地模拟肿瘤环境。我们测试了15纳米GNP和50纳米GNP在两种癌细胞系CAL-27和HeLa的单层细胞和球体上的摄取情况，以评估在相似条件下2D和3D模型之间的差异。还使用了可作为放射增敏剂的抗癌药物多西他赛（DTX），这为GNP介导的联合疗法的未来潜力提供了信息。在2D单层模型中，添加DTX导致GNP摄取量有小幅、不显著的增加，增幅在13%至24%之间，而在3D球体模型中，DTX使摄取量增加了47%至186%，相对于HeLa，CAL-27的增加幅度要大得多。此外，对于CAL-27球体，15纳米GNP相对于50纳米GNP的穿透深度增加了33%，对于HeLa球体则增加了17%。这些结果凸显了在更逼真的肿瘤生存环境中优化GNP治疗条件的必要性。3D球体模型可以捕捉到重要细节，比如不同癌细胞系的不同堆积密度，而简单的2D单层模型则没有这些细节。
