Departamento de Biología Molecular, Facultad de Ciencias Exactas Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto (UNRC), Río Cuarto 5800, Córdoba, Argentina.
Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados (IITEMA), UNRC y Consejo Nacional de, Investigaciones Científicas y Tecnológicas (CONICET), Río Cuarto 5800, Córdoba, Argentina.; Departamento de Química, Facultad de Ciencias Exactas Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto (UNRC), Río Cuarto 5800, Córdoba, Argentina.
J Photochem Photobiol B. 2020 Nov;212:112045. doi: 10.1016/j.jphotobiol.2020.112045. Epub 2020 Oct 1.
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.
由于共轭聚合物纳米粒子具有优异的光吸收和光稳定性，因此它们是光敏剂（PS）的有前途的候选者，可用于光动力疗法（PDT）。最近，我们开发了金属化卟啉掺杂共轭聚合物纳米粒子（CPN）用于 PDT，这些纳米粒子通过活性氧（ROS）介导的凋亡性质的光诱导损伤有效地消除肿瘤细胞。这些纳米聚集体作为密集堆积的多发色团体系，具有出色的光捕获和（颗粒内）能量转移能力，从而有效地形成 ROS 光敏化。一般来说，在预测 PDT 结果时，需要考虑三个关键因素：光、PS 和氧气。然而，最近的研究发现胶质母细胞瘤（GBM）细胞之间存在深刻的遗传异质性，包括对 ROS 的适应。因此，在设计 PDT 方案以预测其结果时，必须考虑肿瘤异质性及其对产生 ROS 的治疗剂的敏感性差异。在这项研究中，通过 CPN 介导的 PDT 使用三种具有不同初始氧化还原状态的 GBM 细胞系比较了通过 ROS 介导的抗癌活性。T98G 细胞最有效地结合纳米粒子，但对 CPN-PDT 效应的抵抗力也最强。部分原因是这些细胞中通过基因表达分析测量到的基础和 PDT 诱导的抗氧化酶水平存在差异。此外，考虑到细胞特异性抗氧化酶状态是 GBM 异质性的重要特征，确定其与 CPN-PDT 结果的相关性对于设计新型和改进的基于 CPN 的治疗方法可能很重要。
