Synergetic effects in mechanisms are important for successful combination therapy. Herein, we used buthionine sulfoximine (BSO) to reduce the cytosolic concentration of glutathione (GSH), a natural scavenger of reactive oxygen species (ROS). We then performed photodynamic therapy (PDT) using chlorin e6-loaded poly(ethylene glycol)-block-poly(D,L lactide) nanoparticles (Ce6-PEG-PLA-NPs). Upon laser irradiation, cytotoxic ROS generated from Ce6-PEG-PLA-NPs killed tumor cells effectively due to the reduced concentration of GSH with addition of BSO. When intravenously injected into tumor-bearing mice, Ce6-PEG-PLA-NPs resulted in efficient delivery of Ce6 to tumor tissues, as shown in near-infrared fluorescence (NIRF) imaging. The accumulation of Ce6 in tumor tissue was more than 2 folds increased by Ce6-PEG-PLA-NPs at every time points. The synergetic effect of reduced GSH synthesis by BSO and efficient delivery of Ce6-PEG-PLA-NPs to tumor tissue was observed in a mouse model after laser irradiation. The combination of BSO and Ce6-PEG-PLA-NPs resulted in complete suppression of tumor, while BSO or Ce6-PEG-PLA-NPs-treated tumors grew to about 1800 and 400 mm³, respectively. The overall results suggest that the combination of BSO and photosensitizer-loaded NPs is effective and demonstrates promise for tumor therapy.

机制中的协同作用对于成功的联合治疗很重要。在本文中，我们使用了丁硫氨酸亚砜亚胺（BSO）来降低谷胱甘肽（GSH）（一种活性氧（ROS）的天然清除剂）的胞浆浓度。然后，我们使用负载二氢卟酚e6的聚（乙二醇）-嵌段-聚（D，L丙交酯）纳米粒子（Ce6-PEG-PLA-NPs）进行了光动力疗法（PDT）。激光照射后，由于添加BSO降低了GSH的浓度，Ce6-PEG-PLA-NPs产生的细胞毒性ROS有效杀死了肿瘤细胞。如近红外荧光（NIRF）成像所示，当将Ce6-PEG-PLA-NP静脉内注射到荷瘤小鼠中时，可将Ce6有效递送到肿瘤组织。在每个时间点，Ce6-PEG-PLA-NPs在肿瘤组织中的Ce6积累增加了2倍以上。在激光照射后的小鼠模型中观察到BSO减少GSH合成的协同作用以及Ce6-PEG-PLA-NPs有效递送至肿瘤组织的协同作用。BSO和Ce6-PEG-PLA-NPs的组合可完全抑制肿瘤，而BSO或Ce6-PEG-PLA-NPs处理的肿瘤长至1800和400 mm³，分别。总体结果表明，BSO和负载有光敏剂的NP的组合是有效的，并证明了对肿瘤治疗的希望。