To clarify the possible mechanisms of α anordin and probimane on calmodulin Ca ++ Mg ++ APTase system, enzyme dynamic study was carried out by determining three dynamic parameters [the substrate concentra...To clarify the possible mechanisms of α anordin and probimane on calmodulin Ca ++ Mg ++ APTase system, enzyme dynamic study was carried out by determining three dynamic parameters [the substrate concentration(ATP) response curve, dose(inhibitors) response curve and time response curve]. Our data have shown that the inhibitory rates of α anordrin and probimane are unrelated to substrate(APT) concentrations, but related to calmodulin concentrations. The inhibition of α anordrin and probimane is very quick that is completed within 1 to 5 min and can maintain more than 1 hr in the same inhibitory rates. So it is possible that α anordrin and probimane are calmodulin competitors with calmodulin like binding whose actions can occur by affecting the reaction balance of substrate and product on target enzymes of calmodulin( Ca ++ Mg ++ ATPase).展开更多
The enzyme-mediated elevation of reactive oxygen species(ROS)at the tumor sites has become an emerging strategy for regulating intracellular redox status for anticancer treatment.Herein,we proposed a camouflaged bioni...The enzyme-mediated elevation of reactive oxygen species(ROS)at the tumor sites has become an emerging strategy for regulating intracellular redox status for anticancer treatment.Herein,we proposed a camouflaged bionic cascaded-enzyme nanoreactor based on Ti_(3)C_(2)nanosheets for combined tumor enzyme dynamic therapy(EDT),phototherapy and deoxygenation-activated chemotherapy.Briefly,glucose oxidase(GOX)and chloroperoxidase(CPO)were chemically conjugated onto Ti_(3)C_(2)nanosheets,where the deoxygenation-activated drug tirapazamine(TPZ)was also loaded,and the Ti_(3)C_(2)-GOX-CPO/TPZ(TGCT)was embedded into nanosized cancer cell-derived membrane vesicles with high-expressed CD47(m_eTGCT).Due to biomimetic membrane camouflage and CD47 overexpression,m_eTGCT exhibited superior immune escape and homologous targeting capacities,which could effectively enhance the tumor preferential targeting and internalization.Once internalized into tumor cells,the cascade reaction of GOX and CPO could generate HClO for efficient EDT.Simultaneously,additional laser irradiation could accelerate the enzymic-catalytic reaction rate and increase the generation of singlet oxygen(~1O_(2)).Furthermore,local hypoxia environment with the oxygen depletion by EDT would activate deoxygenation-sensitive prodrug for additional chemotherapy.Consequently,m_eTGCT exhibits amplified synergistic therapeutic effects of tumor phototherapy,EDT and chemotherapy for efficient tumor inhibition.This intelligent cascaded-enzyme nanoreactor provides a promising approach to achieve concurrent and significant antitumor therapy.展开更多
文摘To clarify the possible mechanisms of α anordin and probimane on calmodulin Ca ++ Mg ++ APTase system, enzyme dynamic study was carried out by determining three dynamic parameters [the substrate concentration(ATP) response curve, dose(inhibitors) response curve and time response curve]. Our data have shown that the inhibitory rates of α anordrin and probimane are unrelated to substrate(APT) concentrations, but related to calmodulin concentrations. The inhibition of α anordrin and probimane is very quick that is completed within 1 to 5 min and can maintain more than 1 hr in the same inhibitory rates. So it is possible that α anordrin and probimane are calmodulin competitors with calmodulin like binding whose actions can occur by affecting the reaction balance of substrate and product on target enzymes of calmodulin( Ca ++ Mg ++ ATPase).
基金This work was supported by the National Natural Science Foundation of China(51773231)Shenzhen Science and Technology Project(JCYJ20190807160801664)the Project of Key Laboratory of Sensing Technology and Biomedical Instruments of Guangdong Province(2011A060901013).
文摘The enzyme-mediated elevation of reactive oxygen species(ROS)at the tumor sites has become an emerging strategy for regulating intracellular redox status for anticancer treatment.Herein,we proposed a camouflaged bionic cascaded-enzyme nanoreactor based on Ti_(3)C_(2)nanosheets for combined tumor enzyme dynamic therapy(EDT),phototherapy and deoxygenation-activated chemotherapy.Briefly,glucose oxidase(GOX)and chloroperoxidase(CPO)were chemically conjugated onto Ti_(3)C_(2)nanosheets,where the deoxygenation-activated drug tirapazamine(TPZ)was also loaded,and the Ti_(3)C_(2)-GOX-CPO/TPZ(TGCT)was embedded into nanosized cancer cell-derived membrane vesicles with high-expressed CD47(m_eTGCT).Due to biomimetic membrane camouflage and CD47 overexpression,m_eTGCT exhibited superior immune escape and homologous targeting capacities,which could effectively enhance the tumor preferential targeting and internalization.Once internalized into tumor cells,the cascade reaction of GOX and CPO could generate HClO for efficient EDT.Simultaneously,additional laser irradiation could accelerate the enzymic-catalytic reaction rate and increase the generation of singlet oxygen(~1O_(2)).Furthermore,local hypoxia environment with the oxygen depletion by EDT would activate deoxygenation-sensitive prodrug for additional chemotherapy.Consequently,m_eTGCT exhibits amplified synergistic therapeutic effects of tumor phototherapy,EDT and chemotherapy for efficient tumor inhibition.This intelligent cascaded-enzyme nanoreactor provides a promising approach to achieve concurrent and significant antitumor therapy.
