Enzymes are an important tool used for signal amplification in biosensing.However,traditional amplification methods based on enzymes are always dependent on their catalytic activities,so their signals fluctuate with t...Enzymes are an important tool used for signal amplification in biosensing.However,traditional amplification methods based on enzymes are always dependent on their catalytic activities,so their signals fluctuate with the change of micro-environment(e.g.,pH and temperature).In this work,we communicate an activity-independent enzyme-powered(AIEP)amplification strategy for biosensing to improve signal stability and fidelity.To verify this hypothesis,the monitoring of oxidative stress during drug-induced liver injury was carried out.Carboxylesterase(CEs),highly expressed in hepatic tissue,was selected as the amplification tool.A CEs configuration-matching fluorophore(CMF)was designed and screened,and a nanobeacon was fabricated by loading CMF within an O_(2)^(•-)-responsive polymeric micelle.Since the degradation of the nanobeacon was triggered by O_(2)^(•-),CMF was released to bind with CEs,and the fluorescence was lit by CEs-CMF configuration matching but not catalytic reaction.Results demonstrated that the oxidative stress during drug-induced liver injury could be successfully monitored,and the hepatoprotective effects of repair drugs could be evaluated by cell and in vivo imaging.This strategy is flexible for bioactive molecules by altering the responsive unit and generally accessible for pharmacological evaluation.展开更多
Solid tumors always exhibit local hypoxia,resulting in the high metastasis and inertness to chemotherapy.Reconstruction of hypoxic tumor microenvironment(TME)is considered a potential therapy compared to directly kill...Solid tumors always exhibit local hypoxia,resulting in the high metastasis and inertness to chemotherapy.Reconstruction of hypoxic tumor microenvironment(TME)is considered a potential therapy compared to directly killing tumor cells.However,the insufficient oxygen delivery to deep tumor and the confronting Warburg effect"compromise the efficacy of hypoxia alleviation.Herein,we construct a cascade enzyme-powered nanomotor(NM-si),which can simultaneously provide sufficient oxygen in deep tumor and inhibit the aerobic glycolysis to potentiate anti-metastasis in chemotherapy.Catalase(Cat)and glucose oxidase(GOx)are co-adsorbed on our previously reported CAuNCs@HA to form self-propelled nanomotor(NM),with hexokinase-2(HK-2)siRNA further condensed(NM-si).The persistent production of oxygen bubbles from the cascade enzymatic reaction propels NM-si to move forward autonomously and in a controllable direction along H_(2)O_(2) gradient towards deep tumor,with hypoxia successfully alleviated in the meantime.The autonomous movement also facilitates NM-si with lysosome escaping for efficient HK-2 knockdown to inhibit glycolysis.In vivo results demonstrated a promising anti-metastasis effect of commercially available albumin-bound paclitaxel(PTX@HSA)after pre-treated with NM-si for TME reconstruction.This cascade enzyme-powered nanomotor provides a potential prospect in reversing the hypoxic TME and metabolic pathway for reinforced anti-metastasis of chemotherapy.展开更多
基金supported by National Natural Science Foundation of China(22222402,21735001,21974013,32001782)Changsha Municipal Natural Science Foundation(kq2208216)+1 种基金the Open Fund of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University(2021018)the Scientific Research Fund of the Hunan Provincial Education Department(23B0308).
文摘Enzymes are an important tool used for signal amplification in biosensing.However,traditional amplification methods based on enzymes are always dependent on their catalytic activities,so their signals fluctuate with the change of micro-environment(e.g.,pH and temperature).In this work,we communicate an activity-independent enzyme-powered(AIEP)amplification strategy for biosensing to improve signal stability and fidelity.To verify this hypothesis,the monitoring of oxidative stress during drug-induced liver injury was carried out.Carboxylesterase(CEs),highly expressed in hepatic tissue,was selected as the amplification tool.A CEs configuration-matching fluorophore(CMF)was designed and screened,and a nanobeacon was fabricated by loading CMF within an O_(2)^(•-)-responsive polymeric micelle.Since the degradation of the nanobeacon was triggered by O_(2)^(•-),CMF was released to bind with CEs,and the fluorescence was lit by CEs-CMF configuration matching but not catalytic reaction.Results demonstrated that the oxidative stress during drug-induced liver injury could be successfully monitored,and the hepatoprotective effects of repair drugs could be evaluated by cell and in vivo imaging.This strategy is flexible for bioactive molecules by altering the responsive unit and generally accessible for pharmacological evaluation.
基金supported by National Natural Science Foundation of China(No.81961138009)the Fundamental Research Funds for the Central Universities(Nos.SCU2017A001,2018SCUH0024,China)+1 种基金111 Project(No.B18035,China)the Key Research and Development Program of Science and Technology Department of Sichuan Province(No.2020YFS0570,China)
文摘Solid tumors always exhibit local hypoxia,resulting in the high metastasis and inertness to chemotherapy.Reconstruction of hypoxic tumor microenvironment(TME)is considered a potential therapy compared to directly killing tumor cells.However,the insufficient oxygen delivery to deep tumor and the confronting Warburg effect"compromise the efficacy of hypoxia alleviation.Herein,we construct a cascade enzyme-powered nanomotor(NM-si),which can simultaneously provide sufficient oxygen in deep tumor and inhibit the aerobic glycolysis to potentiate anti-metastasis in chemotherapy.Catalase(Cat)and glucose oxidase(GOx)are co-adsorbed on our previously reported CAuNCs@HA to form self-propelled nanomotor(NM),with hexokinase-2(HK-2)siRNA further condensed(NM-si).The persistent production of oxygen bubbles from the cascade enzymatic reaction propels NM-si to move forward autonomously and in a controllable direction along H_(2)O_(2) gradient towards deep tumor,with hypoxia successfully alleviated in the meantime.The autonomous movement also facilitates NM-si with lysosome escaping for efficient HK-2 knockdown to inhibit glycolysis.In vivo results demonstrated a promising anti-metastasis effect of commercially available albumin-bound paclitaxel(PTX@HSA)after pre-treated with NM-si for TME reconstruction.This cascade enzyme-powered nanomotor provides a potential prospect in reversing the hypoxic TME and metabolic pathway for reinforced anti-metastasis of chemotherapy.
