Developing customized chemical reactions that could regulate a specific biological process on demand is regarded as an advanced and promising strategy for treating diseases.However,conventional chemical reactions beco...Developing customized chemical reactions that could regulate a specific biological process on demand is regarded as an advanced and promising strategy for treating diseases.However,conventional chemical reactions become challenging in complex physiological environments,which demand mild reaction conditions,high efficiency,good biocompatibility,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 effectively induced apoptosis.We propose a mechanism of the reaction where PFP is photoexcited to PFP*,and the obtained photoelectrons are transferred from PFP*to NAD+to produce nicotinamide and another unstable intermediate,ADP-ribosyl radical.ADP-ribosyl radical quickly reacts with triethanolamine 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.展开更多
基金supported by the National Natural Science Foundation of China(grant nos.22021002,22020102005,and 22022705)CAS-Croucher Funding Scheme for Joint Laboratories,and K.C.Wong Education Foundation(grant no.GJTD-2020-02).
文摘Developing customized chemical reactions that could regulate a specific biological process on demand is regarded as an advanced and promising strategy for treating diseases.However,conventional chemical reactions become challenging in complex physiological environments,which demand mild reaction conditions,high efficiency,good biocompatibility,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 effectively induced apoptosis.We propose a mechanism of the reaction where PFP is photoexcited to PFP*,and the obtained photoelectrons are transferred from PFP*to NAD+to produce nicotinamide and another unstable intermediate,ADP-ribosyl radical.ADP-ribosyl radical quickly reacts with triethanolamine 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.