The novel concept of enzyme photocatalysis has recently attracted much attention in developing anticancer therapy.However,the relationship between coenzyme depletion and cellular metabolomic changes has rarely been in...The novel concept of enzyme photocatalysis has recently attracted much attention in developing anticancer therapy.However,the relationship between coenzyme depletion and cellular metabolomic changes has rarely been investigated.Herein,we report the rational design of a deep-red light-triggered bis-tridentate Ru(Ⅱ)photocatalyst(Ru3),which induces cell metabolism disorder to combat multidrug resistance.Ru3 exhibits promising multiple triplet excited states,a long lifetime,and high photocatalytic activity toward the coenzyme.Consequently,Ru3 shows high phototherapeutic activity(photo index=191–833)against diverse resistant(cisplatin,5-fluorouracil,or paclitaxel)lung cancer cells by inhibiting cellular peptide,lipid,and glycerophospholipid metabolism.We believe that cell metabolism inhibition by photo-redox catalysts is an effective form of therapeutics for drug-resistant cancer cells.展开更多
基金supported by the National Natural Science Foundation of China(22277153,22007104,21975053)Guangdong Basic and Applied Basic Research Foundation(2021B1515020050,2023B1515020060)+3 种基金the Science,Technology and Innovation Commission of Shenzhen Municipality Project(JCYJ20190807152616996)the Fundamental Research Funds for the Central Universities(22lgqb37)the Department of Science&Technology(DST),Government of India(DST/INSPIRE/04/2019/000492)the Royal Society for a Newton International Fellowships Alumni 2021(AL211023)。
文摘The novel concept of enzyme photocatalysis has recently attracted much attention in developing anticancer therapy.However,the relationship between coenzyme depletion and cellular metabolomic changes has rarely been investigated.Herein,we report the rational design of a deep-red light-triggered bis-tridentate Ru(Ⅱ)photocatalyst(Ru3),which induces cell metabolism disorder to combat multidrug resistance.Ru3 exhibits promising multiple triplet excited states,a long lifetime,and high photocatalytic activity toward the coenzyme.Consequently,Ru3 shows high phototherapeutic activity(photo index=191–833)against diverse resistant(cisplatin,5-fluorouracil,or paclitaxel)lung cancer cells by inhibiting cellular peptide,lipid,and glycerophospholipid metabolism.We believe that cell metabolism inhibition by photo-redox catalysts is an effective form of therapeutics for drug-resistant cancer cells.