Morpholinoethoxy-Substituted Cationic Metal-Free and Metallo Phthalocyanines: In Vitro Photodynamic Therapy Activities, PDT-Induced ROS Level Measurements, and Cellular Death Mechanism
Muge Serhatli*, Seyma Isik, Ayfer Kalkan, Mukaddes Özçeşmeci, Esin Hamuryudan and Özge Can*,
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引用次数: 0
Abstract
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.
期刊介绍:
ACS Bio & Med Chem Au is a broad scope open access journal which publishes short letters comprehensive articles reviews and perspectives in all aspects of biological and medicinal chemistry. Studies providing fundamental insights or describing novel syntheses as well as clinical or other applications-based work are welcomed.This broad scope includes experimental and theoretical studies on the chemical physical mechanistic and/or structural basis of biological or cell function in all domains of life. It encompasses the fields of chemical biology synthetic biology disease biology cell biology agriculture and food natural products research nucleic acid biology neuroscience structural biology and biophysics.The journal publishes studies that pertain to a broad range of medicinal chemistry including compound design and optimization biological evaluation molecular mechanistic understanding of drug delivery and drug delivery systems imaging agents and pharmacology and translational science of both small and large bioactive molecules. Novel computational cheminformatics and structural studies for the identification (or structure-activity relationship analysis) of bioactive molecules ligands and their targets are also welcome. The journal will consider computational studies applying established computational methods but only in combination with novel and original experimental data (e.g. in cases where new compounds have been designed and tested).Also included in the scope of the journal are articles relating to infectious diseases research on pathogens host-pathogen interactions therapeutics diagnostics vaccines drug-delivery systems and other biomedical technology development pertaining to infectious diseases.