Singlet Oxygen Photo-Generation by Light Irradiation Using Metal–Organic Frameworks as Photodynamic Therapy Agents

A metal–organic-framework zirconium (pyrene-1,3,6,8-tetryl)tetrabenzoic acid (Zr7Pr) was fabricated and evaluated in retinal pigmented epithelial cells in vitro for singlet oxygen inactivation of cell function. Cellular health was evaluated through the measurement of stress biomarkers. It was shown that increases in lactate dehydrogenase (LDH) and mitochondrial membrane potential (MMP) activity are consistent with singlet reactive oxygen species (ROS). The levels of nitric oxide (NO) and peroxynitrite (ONOO−) as possible reactive nitrogen species (RNS) were evaluated to identify the site of Zr7Pr’s inhibitory function. The analysis indicates that singlet oxygen generates superoxide and nitric oxide, which generates peroxynitrite. The most likely site of action of Zr7Pr is through the inactivation of mitochondrial pore transitions (MPTs) rather than complete membrane peroxidation. The exposed cysteines or histidine in the molecular targets of MPTs are modified, which affects the cell’s ability to regulate apoptosis-inducing MPTs under oxidative stress. Cells tolerant to hydrogen peroxide poisoning are still susceptible to the actions of Zr7Pr, whose efficacy is most likely through impairment of mitochondrial function and modification of the pore within the adenosine nucleotide translocase protein family (ANT) domain of the MPT.