Horne Tamarisk K, Cronjé Marianne J
Dept of Biochemistry, Faculty of Science, University of Johannesburg, Auckland Park, 2006, Gauteng, South Africa.
Dept of Biochemistry, Faculty of Science, University of Johannesburg, Auckland Park, 2006, Gauteng, South Africa.
J Photochem Photobiol B. 2017 Aug;173:412-422. doi: 10.1016/j.jphotobiol.2017.06.013. Epub 2017 Jun 12.
A longstanding obstacle to cancer eradication centers on the heterogeneous nature of the tissue that manifests it. Variations between cancer cell resistance profiles often result in a survival percentage following classic therapeutics. As an alternative, photodynamic therapys' (PDT) unique non-specific cell damage mechanism and high degree of application control enables it to potentially deliver an efficient treatment regime to a broad range of heterogeneous tissue types thereby overcoming individual resistance profiles. This study follows on from previous design, characterization and solubility analyses of three novel carbohydrate-ligated zinc-porphyrazine (Zn(II)Pz) derivatives. Here we report on their PDT application potential in the treatment of five common cancer tissue types in vitro. Following analyses of metabolic homeostasis, toxicity and cell death induction, overall Zn(II)Pz-PDT proved comparably efficient between all cancer tissue populations. Differential localization patterns of Zn(II)Pz derivatives between cell types did not appear to influence the overall PDT effect. All cell types exhibited significant disruptions to mitochondrial activity and associated ATP production levels. Toxicity and chromatin structure profiles revealed indiscernible patterns of damage between Zn(II)Pz derivatives and cell type. The subtle differences observed between individual Zn(II)Pz derivatives is most likely due to a combination of carbohydrate moiety characteristics on energy transfer processes and associated dosage optimization requirements per tissue type. Collectively, this indicates that resistance profiles are negated to a significant extent by Zn(II)Pz-PDT making these derivatives attractive candidates for PDT applications across multiple tissue types and subtypes.
根除癌症的一个长期障碍集中在表现出癌症的组织的异质性上。癌细胞耐药性特征之间的差异往往导致经典治疗后的存活率。作为一种替代方案，光动力疗法（PDT）独特的非特异性细胞损伤机制和高度的应用可控性使其有可能为广泛的异质组织类型提供有效的治疗方案，从而克服个体耐药性特征。本研究延续了之前对三种新型碳水化合物连接锌卟啉（Zn(II)Pz）衍生物的设计、表征和溶解性分析。在此，我们报告它们在体外治疗五种常见癌症组织类型中的光动力疗法应用潜力。在对代谢稳态、毒性和细胞死亡诱导进行分析后，总体而言，Zn(II)Pz-PDT在所有癌症组织群体中证明具有相当的效率。Zn(II)Pz衍生物在细胞类型之间的差异定位模式似乎并未影响整体光动力疗法效果。所有细胞类型的线粒体活性和相关的ATP产生水平均表现出显著破坏。毒性和染色质结构特征显示Zn(II)Pz衍生物与细胞类型之间的损伤模式难以区分。在各个Zn(II)Pz衍生物之间观察到的细微差异很可能是由于碳水化合物部分特征对能量转移过程的综合影响以及每种组织类型相关的剂量优化要求。总体而言，这表明Zn(II)Pz-PDT在很大程度上消除了耐药性特征，使这些衍生物成为跨多种组织类型和亚型的光动力疗法应用的有吸引力的候选物。
