Photodynamic Therapy (PDT) offers an alternative option for the treatment of nasopharyngeal carcinoma (NPC). The utilization of 3-dimensional (3D) culture model might provide better understanding of PDT effects on NPC cells. The aim of this in vitro study was to compare PDT effect on NPC cells using 2D and 3D models.

Two 3D culture models were established using liquid overlay method with agarose base (MCL) and hanging drop method (MCS). PDT was carried out using the combination of FosPeg® and 652 nm laser in 3D and conventional 2D models. The effects of 3D culture size and morphology on the uptake and distribution of sensitizer and gene expression were examined. Photocytotoxity, mode of cell death, and protein expression were compared for 2D and 3D models.

Regular and irregular NPC spheroids were obtained from MCL and MCS methods, respectively. A significantly down-regulation of LMP1 mRNA were observed in MCL spheroid. The sensitizer uptake in 3D spheroids was half of 2D culture. More sensitizers were required to obtain IC₅₀ in 3D spheroids. Apoptosis, necrosis and autophagosomes were detected in PDT treated 2D and 3D cells. Different protein expression patterns were observed in 2D and 3D models.

FosPeg® PDT is effective in killing NPC cells. MCL-derived 3D spheroid model is more suitable for the evaluation of PDT killing mechanisms.

光动力疗法（PDT）为鼻咽癌（NPC）的治疗提供了另一种选择。三维（3D）培养模型的利用可能会更好地了解PDT对NPC细胞的作用。这项体外研究的目的是使用2D和3D模型比较PDT对NPC细胞的作用。

使用带琼脂糖基的液体覆盖法（MCL）和悬滴法（MCS）建立了两个3D培养模型。在3D和常规2D模型中，结合使用FosPeg®和652 nm激光进行PDT。检查了3D培养物大小和形态对敏化剂摄取和分布以及基因表达的影响。比较了2D和3D模型的光细胞毒性，细胞死亡模式和蛋白质表达。

规则和不规则NPC球体分别从MCL和MCS方法获得。在MCL球体中观察到LMP1 mRNA的显着下调。3D球体中敏化剂的摄取量是2D培养物的一半。需要更多的敏化剂才能获得3D球体的IC ₅₀。在PDT处理的2D和3D细胞中检测到凋亡，坏死和自噬体。在2D和3D模型中观察到了不同的蛋白质表达模式。

FosPeg®PDT可有效杀死NPC细胞。MCL衍生的3D球体模型更适合用于评估PDT杀死机制。