Transmembrane anion transporters have attracted significant attention as therapeutic agents because of their potential to disrupt cellular ion homeostasis,in which,most of the synthetic anionic transporters are organi...Transmembrane anion transporters have attracted significant attention as therapeutic agents because of their potential to disrupt cellular ion homeostasis,in which,most of the synthetic anionic transporters are organic small molecules whose synthesis routes are usually complex and tedious,and the related biological research is also only in infancy.Hence,we synthesized a kind of chloride anion(Cl-)and sodium cation(Na^+)nanocarrier based on poly(D,L-lactic-co-glycolic acid)(PLGA)which was coated with polydopamine(PDA)to provide target release factor.When the nanocarrier arrives in acidic enviro nment such as lysosomes through endocytosis,Cl^-and Na^+will be released fast from the nanocarrier resulting in imbalance of cell homeostasis for inducing apoptosis.Cell experiments show that the nanocarrier promotes apoptosis and leads to an increased concentration of reactive oxygen species.By exploring the concentration of cytochrome c in mitochondria and cytoplasm and the activities of key enzymes caspase-9 and caspase-3 in apoptosis process,it is proved that the apoptotic pathway is caspase-dependent.This novel strategy allows the research of anion transporter no longer limited to artificial synthesis of small molecular and provides a novel and effective direction to investigate ion homeostasis,ion transport and cancer treatment.展开更多
基金financially supported by the National Natural Science Foundation of China(No.21575055)。
文摘Transmembrane anion transporters have attracted significant attention as therapeutic agents because of their potential to disrupt cellular ion homeostasis,in which,most of the synthetic anionic transporters are organic small molecules whose synthesis routes are usually complex and tedious,and the related biological research is also only in infancy.Hence,we synthesized a kind of chloride anion(Cl-)and sodium cation(Na^+)nanocarrier based on poly(D,L-lactic-co-glycolic acid)(PLGA)which was coated with polydopamine(PDA)to provide target release factor.When the nanocarrier arrives in acidic enviro nment such as lysosomes through endocytosis,Cl^-and Na^+will be released fast from the nanocarrier resulting in imbalance of cell homeostasis for inducing apoptosis.Cell experiments show that the nanocarrier promotes apoptosis and leads to an increased concentration of reactive oxygen species.By exploring the concentration of cytochrome c in mitochondria and cytoplasm and the activities of key enzymes caspase-9 and caspase-3 in apoptosis process,it is proved that the apoptotic pathway is caspase-dependent.This novel strategy allows the research of anion transporter no longer limited to artificial synthesis of small molecular and provides a novel and effective direction to investigate ion homeostasis,ion transport and cancer treatment.
