Metal complexes continue to be an exciting avenue in the quest for novel therapeutics to treat malignant tumours.This is due to their versatile coordination chemistry,tunable redox activity,and distinct mechanisms of ...Metal complexes continue to be an exciting avenue in the quest for novel therapeutics to treat malignant tumours.This is due to their versatile coordination chemistry,tunable redox activity,and distinct mechanisms of action.Cancer cells proliferate by adopting various metabolic pathways to fulfil their bioenergetic and biosynthetic demands.These altered metabolic pathways also contribute to substantial resistance to clinically approved drugs such as cisplatin.Therefore,designing therapeutic agents targeting specific metabolic pathways in tumours is a promising approach and has been widely explored in recent years.In this perspective,we provide a detailed mechanistic overview of the state-of-the-art progress of metalbased compounds that target cancer bioenergetics and various metabolic pathways to inhibit cancer progression.We also provide a comprehensive analysis of the most relevant metal complexes that concurrently target metabolic pathways and stimulate immunological response,thereby eliciting a synergistic effect that enhances treatment efficacy and overcomes drug resistance issues.Gaining insights into the structural features of these metal-based compounds will open a new therapeutic window to treat nasty tumours.展开更多
Traditional chemotherapeutic approaches lack selectivity and damage both cancerous and healthy cells.In contrast,cancer immunotherapy harnesses the host's immune system to selectively target and eradicate tumor ce...Traditional chemotherapeutic approaches lack selectivity and damage both cancerous and healthy cells.In contrast,cancer immunotherapy harnesses the host's immune system to selectively target and eradicate tumor cells,offering tremendous potential for the long-term suppression of tumor growth and preventing its recurrence.However,tumors often develop immune evasion by exploiting immune checkpoints,which regulate the immune system.Among these checkpoints,programmed death protein 1(PD-1)and its ligand(PD-L1)have garnered significant interest because they play a key role in protecting the tumor cells from immune-mediated eradication.The approval of monoclonal antibodies(mAbs)that target PD-1/PDL1 by the Food and Drug Administration(FDA)is a milestone in immunotherapy.Although mAbs have demonstrated remarkable success in treating skin melanomas,their efficacy against other solid tumors remains limited.There is a clear need to explore new approaches to enhance the efficacy of mAbs and find more effective checkpoint inhibitors.Metal-based drugs offer a new platform to address this challenge.This review highlights the recent progress in leveraging metal complexes as PD-1/PD-L1 inhibitors.We discussed metal-based agents used either alone or in combination with mAbs to boost the immune system.We also highlighted examples of metallodrugs encapsulated within the nanoparticles to augment the efficacy of immune checkpoint therapy.While research on metal-based complexes targeting PD-1/PDL1 is still in its infancy,the examples presented here will serve as the basis for future discussions and efforts in this emerging field.We anticipate that ongoing research in targeting immune checkpoint blockade with innovative metal-based therapeutics will enhance the scope of treatment across a wide range of cancers.展开更多
基金supported by the Fundamental Research Funds for the Central Universities(M.N.)and the National Natural Science Foundation of China(grant U22A20347)the Health Research Council of New Zealand for a Sir Charles Hercus Fellowship(M.H.,20/069).
文摘Metal complexes continue to be an exciting avenue in the quest for novel therapeutics to treat malignant tumours.This is due to their versatile coordination chemistry,tunable redox activity,and distinct mechanisms of action.Cancer cells proliferate by adopting various metabolic pathways to fulfil their bioenergetic and biosynthetic demands.These altered metabolic pathways also contribute to substantial resistance to clinically approved drugs such as cisplatin.Therefore,designing therapeutic agents targeting specific metabolic pathways in tumours is a promising approach and has been widely explored in recent years.In this perspective,we provide a detailed mechanistic overview of the state-of-the-art progress of metalbased compounds that target cancer bioenergetics and various metabolic pathways to inhibit cancer progression.We also provide a comprehensive analysis of the most relevant metal complexes that concurrently target metabolic pathways and stimulate immunological response,thereby eliciting a synergistic effect that enhances treatment efficacy and overcomes drug resistance issues.Gaining insights into the structural features of these metal-based compounds will open a new therapeutic window to treat nasty tumours.
基金supported by the Fundamental Research Funds for the Central Universitiesthe National Natural Science Foundation of China(No.U22A20347)the Health Research Council of New Zealand for a Sir Charles Hercus Fellowship(M.H.)。
文摘Traditional chemotherapeutic approaches lack selectivity and damage both cancerous and healthy cells.In contrast,cancer immunotherapy harnesses the host's immune system to selectively target and eradicate tumor cells,offering tremendous potential for the long-term suppression of tumor growth and preventing its recurrence.However,tumors often develop immune evasion by exploiting immune checkpoints,which regulate the immune system.Among these checkpoints,programmed death protein 1(PD-1)and its ligand(PD-L1)have garnered significant interest because they play a key role in protecting the tumor cells from immune-mediated eradication.The approval of monoclonal antibodies(mAbs)that target PD-1/PDL1 by the Food and Drug Administration(FDA)is a milestone in immunotherapy.Although mAbs have demonstrated remarkable success in treating skin melanomas,their efficacy against other solid tumors remains limited.There is a clear need to explore new approaches to enhance the efficacy of mAbs and find more effective checkpoint inhibitors.Metal-based drugs offer a new platform to address this challenge.This review highlights the recent progress in leveraging metal complexes as PD-1/PD-L1 inhibitors.We discussed metal-based agents used either alone or in combination with mAbs to boost the immune system.We also highlighted examples of metallodrugs encapsulated within the nanoparticles to augment the efficacy of immune checkpoint therapy.While research on metal-based complexes targeting PD-1/PDL1 is still in its infancy,the examples presented here will serve as the basis for future discussions and efforts in this emerging field.We anticipate that ongoing research in targeting immune checkpoint blockade with innovative metal-based therapeutics will enhance the scope of treatment across a wide range of cancers.
