Bannister Aaron, Dissanayake Dushanthi, Kowalewski Antonia, Cicon Leah, Bromma Kyle, Chithrani Devika B
Department of Physics and Astronomy, University of Victoria, Victoria, BC V8P 5C2, Canada.
Department of Physics, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.
Bioengineering (Basel). 2020 Jun 14;7(2):56. doi: 10.3390/bioengineering7020056.
Nanoparticles (NPs) have shown promise in both radiotherapy and chemotherapy. NPs are mainly transported along cellular microtubules (MTs). Docetaxel (DTX) is a commonly used chemotherapeutic drug that can manipulate the cellular MT network to maximize its clinical benefit. However, the effect of DTX on NP behaviour has not yet been fully elucidated. We used gold NPs of diameters 15 and 50 nm at a concentration of 0.2 nM to investigate the size dependence of NP behaviour. Meanwhile, DTX concentrations of 0, 10 and 50 nM were used to uphold clinical relevance. Our study reveals that a concentration of 50 nM DTX increased NP uptake by ~50% and their retention by ~90% compared to cells treated with 0 and 10 nM DTX. Smaller NPs had a 20-fold higher uptake in cells treated with 50 nM DTX vs. 0 and 10 nM DTX. With the treatment of 50 nm DTX, the cells became more spherical in shape, and NPs were redistributed closer to the nucleus. A significant increase in NP uptake and retention along with their intracellular distribution closer to the nucleus with 50 nM DTX could be exploited to target a higher dose to the most important target, the nucleus in both radiotherapy and chemotherapy.
纳米颗粒（NPs）在放射治疗和化学治疗中均显示出应用前景。NPs主要沿细胞微管（MTs）运输。多西他赛（DTX）是一种常用的化疗药物，可操控细胞MT网络以最大化其临床益处。然而，DTX对NP行为的影响尚未完全阐明。我们使用直径为15和50 nm、浓度为0.2 nM的金纳米颗粒来研究NP行为的尺寸依赖性。同时，使用0、10和50 nM的DTX浓度以符合临床实际情况。我们的研究表明，与用0和10 nM DTX处理的细胞相比，50 nM DTX浓度使NP摄取增加了约50%，其滞留增加了约90%。在用50 nM DTX处理的细胞中，较小的NP摄取量比用0和10 nM DTX处理的细胞高20倍。用50 nM DTX处理后，细胞形状变得更接近球形，且NP重新分布得更靠近细胞核。50 nM DTX使NP摄取和滞留显著增加，以及它们在细胞内更靠近细胞核的分布，可用于在放射治疗和化学治疗中向最重要的靶点——细胞核靶向更高剂量。
