Regulating antioxidative stress pathways to augment oxidative stress and enhance antitumor therapy is highly desirable but very challenging.Herein,we initiated a multifunctional nanoparticle to regulate the Keap1-Nrf2...Regulating antioxidative stress pathways to augment oxidative stress and enhance antitumor therapy is highly desirable but very challenging.Herein,we initiated a multifunctional nanoparticle to regulate the Keap1-Nrf2 antioxidative stress pathway to promote cancer cell apoptosis.The OPFV-SnMP@GE11 nanoparticles were assembled by enzyme-activated OPFV-TLQ,tin mesoporphyrin(SnMP),and DSPEPEG-GE11.OPFV-SnMP@GE11 accumulated at tumor sites through specific targeting with GE11.OPFV-TLQ was specifically reduced to a photosensitizer OPFVNH2 by endocellular NAD(P)H:quinone oxidoreductase 1(NQO1).Under irradiation,OPFV-NH2 greatly produced reactive oxygen species(ROS)through a type I mechanism,which activated the Keap1-Nrf2 signal pathway and enhanced the transcription of NQO1,resulting in a continuous and explosive generation of ROS.Additionally,SnMP inhibited the activity of heme oxygenase-1(HO-1),further depressing antioxidative stress.This strategy provides insight into the regulation of the signal pathway to amplify oxidative stress,paving the way to studying the molecular mechanisms of cellular activities to enhance cancer therapy.展开更多
A series of near-infrared(NIR)fluorescent substrates(NDRO-1∼8)derived from fluorophore NDRH with different volumes of ester bond as the recognition group were designed and synthesized for the detection of acetylcholi...A series of near-infrared(NIR)fluorescent substrates(NDRO-1∼8)derived from fluorophore NDRH with different volumes of ester bond as the recognition group were designed and synthesized for the detection of acetylcholinesterase(AChE),among which NDRO-1 with the smallest acetate group displayed the highest activity toward AChE.The detection limit of NDRO-1 for sensing AChE was 0.32μg/mL,and K_(m )was 6.40μmol/L,indicating ultra-sensitivity and good affinity of NDRO-1 toward AChE.NDRO-1 was used to detect the inhibitory of four kinds of pesticides including methamidophos,dichlorvos,and the detection limit was lower than 50μg/L,which was further used in pesticide residues detection.展开更多
基金supported by the National Natural Science Foundation of China(grant nos.22274095 and 21974084)the Innovation Capability Support Program of Shaanxi(program no.2021TD-42)the Fundamental Research Funds for the Central Universities(program nos.GK202302004,2021TS030,and GK202101001).
文摘Regulating antioxidative stress pathways to augment oxidative stress and enhance antitumor therapy is highly desirable but very challenging.Herein,we initiated a multifunctional nanoparticle to regulate the Keap1-Nrf2 antioxidative stress pathway to promote cancer cell apoptosis.The OPFV-SnMP@GE11 nanoparticles were assembled by enzyme-activated OPFV-TLQ,tin mesoporphyrin(SnMP),and DSPEPEG-GE11.OPFV-SnMP@GE11 accumulated at tumor sites through specific targeting with GE11.OPFV-TLQ was specifically reduced to a photosensitizer OPFVNH2 by endocellular NAD(P)H:quinone oxidoreductase 1(NQO1).Under irradiation,OPFV-NH2 greatly produced reactive oxygen species(ROS)through a type I mechanism,which activated the Keap1-Nrf2 signal pathway and enhanced the transcription of NQO1,resulting in a continuous and explosive generation of ROS.Additionally,SnMP inhibited the activity of heme oxygenase-1(HO-1),further depressing antioxidative stress.This strategy provides insight into the regulation of the signal pathway to amplify oxidative stress,paving the way to studying the molecular mechanisms of cellular activities to enhance cancer therapy.
基金supported financially by National Key R&D Program of China (No. 2018YFC1603001)
文摘A series of near-infrared(NIR)fluorescent substrates(NDRO-1∼8)derived from fluorophore NDRH with different volumes of ester bond as the recognition group were designed and synthesized for the detection of acetylcholinesterase(AChE),among which NDRO-1 with the smallest acetate group displayed the highest activity toward AChE.The detection limit of NDRO-1 for sensing AChE was 0.32μg/mL,and K_(m )was 6.40μmol/L,indicating ultra-sensitivity and good affinity of NDRO-1 toward AChE.NDRO-1 was used to detect the inhibitory of four kinds of pesticides including methamidophos,dichlorvos,and the detection limit was lower than 50μg/L,which was further used in pesticide residues detection.