Unexpected Photocatalytic Degeneration of NAD+for Inducing Apoptosis of Hypoxia Cancer Cells

Developing customized chemical reactions that could regulate a specific biological process on de-mand is regarded as an advanced and promising strategy for treating diseases. However, conventional chemical reactions become challenging in complex physiological environments, which demand mild re-action conditions, high efficiency, good biocompati-bility, and strong controllability. Moreover, the effects of the achieved reactions on the real biological system are usually further lessened. Herein, we describe an advanced photocatalytic reaction that irreversibly converted nicotinamide adenine dinucleotide (NAD+) to nicotinamide and adenosine diphosphate (ADP)-ribose by the cationic conjugated poly(fluorene-co-phenylene) (PFP). This reaction was introduced to tumor cells and triggered cell apoptosis. Under white-light illumination, the photocatalytic reaction decreased the NAD+ ratio in tumor cells, disrupted the mitochondrial membrane potential, inhibited the synthesis of adenosine triphosphate (ATP), and ef-fectively induced apoptosis. We propose a mecha-nism of the reaction where PFP is photoexcited to PFP*, and the obtained photoelectrons are transferred from PFP* to NAD+ to produce nicotinamide and an-other unstable intermediate, ADP-ribosyl radical. ADP-ribosyl radical quickly reacts with triethanola-mine to form ADP-ribose. This intracellular utilization of a specific photocatalytic reaction could offer a new approach to affect biological function for efficient cancer treatment.