ACS Bio & Med Chem Au最新文献

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Morpholinoethoxy-Substituted Cationic Metal-Free and Metallo Phthalocyanines: In Vitro Photodynamic Therapy Activities, PDT-Induced ROS Level Measurements, and Cellular Death Mechanism 氨基乙氧基取代的阳离子无金属和金属酞菁：体外光动力治疗活性、pdt诱导的ROS水平测量和细胞死亡机制

IF 4.3 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

ACS Bio & Med Chem Au

Pub Date : 2025-06-26 DOI: 10.1021/acsbiomedchemau.5c00137

Muge Serhatli*, Seyma Isik, Ayfer Kalkan, Mukaddes Özçeşmeci, Esin Hamuryudan and Özge Can*,

In this study, morpholinoethoxy-attached cationic tetra-substituted phthalocyanines (Pcs), including metal-free (HQH₂Pc), zinc (HQZnPc), and indium (HQInPc) derivatives, were synthesized following established protocols. Their structures were confirmed by using standard spectroscopic techniques. The photodynamic therapy (PDT) efficacy of these compounds was evaluated against head, neck, and colon cancer cell lines. Reactive oxygen species (ROS) levels induced by PDT with cationic Pcs were quantified by using dichlorodihydrofluorescein diacetate. To elucidate the mechanisms of action, ROS generation was assessed at two distinct time points: 30 min (immediate response) and 24 h (delayed response) post-PDT. The cellular death mechanisms induced by Pc-mediated PDT in cancer cell lines were investigated using fluorescence staining with Apopxin Green, CytoCalcein Violet 450, and 7-AAD to differentiate apoptotic and necrotic pathways and provide insights into the mode of cell death. The results indicated that the Pcs exhibited minimal cytotoxicity in the absence of light, confirming their safety as photosensitizers. Cationic Pcs, particularly HQZnPc, showed high PDT-induced cytotoxicity and ROS production, primarily inducing apoptosis in cancer cell lines, with FaDu cells exhibiting the highest sensitivity. These results highlight HQZnPc’s strong potential for cancer therapy and underscore the need for further research into its delivery and mechanisms in complex tumor models.

在本研究中，我们按照既定的方法合成了无金属（HQH2Pc）、锌（HQZnPc）和铟（HQInPc）的阳离子四取代酞菁（Pcs）衍生物。它们的结构通过标准光谱技术得到了证实。评价了这些化合物对头颈部和结肠癌细胞系的光动力治疗（PDT）效果。采用双乙酸二氯双氢荧光素定量测定阳离子pc PDT诱导的活性氧（ROS）水平。为了阐明作用机制，在两个不同的时间点评估ROS的产生：pdt后30分钟（即时反应）和24小时（延迟反应）。采用Apopxin Green、CytoCalcein Violet 450和7-AAD荧光染色研究pc介导的PDT诱导癌细胞死亡机制，以区分凋亡和坏死途径，为细胞死亡模式提供新的思路。结果表明，Pcs在没有光的情况下表现出最小的细胞毒性，证实了它们作为光敏剂的安全性。阳离子Pcs，特别是HQZnPc，显示出高pdt诱导的细胞毒性和ROS的产生，主要诱导癌细胞凋亡，其中FaDu细胞表现出最高的敏感性。这些结果突出了HQZnPc在癌症治疗方面的强大潜力，并强调了进一步研究其在复杂肿瘤模型中的传递和机制的必要性。

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