Due to their superb light absorption and photostability conjugated polymer nanoparticles are promising photosensitizers (PS) for their use in Photodynamic therapy (PDT). Recently, we developed metallated porphyrin-doped conjugated polymer nanoparticles (CPNs) for PDT that efficiently eliminate tumor cells through reactive oxygen species (ROS) mediated photoinduced damage of apoptotic nature. These nanoaggregates act as densely packed multi-chromophoric systems having exceptional light harvesting and (intra-particle) energy transfer capabilities which lead to efficient photosensitized formation of ROS. In general, three key components; light, PS, and oxygen; are considered in the prediction of the PDT outcome. However, recent studies led to the discovery of a profound genetic heterogeneity among glioblastoma (GBM) cells which include the adaptation to ROS. Thus, tumor heterogeneity and their associated difference in sensitivity to ROS-producing therapeutic agents must be considered in the design of PDT protocols for the prediction of its outcome. In this study, anticancer activity through ROS-mediated PDT using CPNs was compared in three GBM cell lines with different initial redox status. T98G cells were the most effective incorporating nanoparticles but also were the most resistant to CPN-PDT effect. In part, this feature could be attributed to the differential basal and PDT-induced antioxidant enzyme levels found in these cells measured by gene expression analysis. Furthermore, considering that cell-specific antioxidant enzyme status is a significant feature of GBM heterogeneity, establishing its correlation with CPN-PDT outcome might be important for designing novel and improved CPN-based treatments.

由于其极好的光吸收和光稳定性，缀合的聚合物纳米颗粒有望用于光动力疗法（PDT）中。最近，我们开发了用于PDT的金属化掺杂卟啉的共轭聚合物纳米粒子（CPNs），可通过活性氧（ROS）介导的光诱导的凋亡性损伤有效消除肿瘤细胞。这些纳米聚集体充当密集包装的多发色体系，具有出色的光收集和（粒子内）能量转移能力，可导致有效的光敏形成ROS。通常，三个关键部分；光，聚苯乙烯和氧气；在PDT结果的预测中被考虑。然而，最近的研究导致在胶质母细胞瘤（GBM）细胞中发现了深刻的遗传异质性，其中包括对ROS的适应性。因此，在PDT方案设计中必须考虑肿瘤异质性及其对产生ROS的治疗剂敏感性的相关差异，以预测其结果。在这项研究中，在具有不同初始氧化还原状态的三种GBM细胞系中，比较了使用CPNs通过ROS介导的PDT的抗癌活性。T98G细胞是掺入纳米颗粒最有效的方法，但对CPN-PDT的作用也最有抵抗力。部分地，此特征可归因于通过基因表达分析测量的这些细胞中发现的基础和PDT诱导的抗氧化酶水平差异。此外，