Deprivation of glucose and lactate provides an effective pathway to terminate the nutrients supplement for tumor growth.In this work,biomimetic nanozymes called m@BGLC are constructed for catalytic tumor inhibition th...Deprivation of glucose and lactate provides an effective pathway to terminate the nutrients supplement for tumor growth.In this work,biomimetic nanozymes called m@BGLC are constructed for catalytic tumor inhibition through nutrients deprivation and oxidative damage induction.Concretely,the catalytic enzymes of glucose oxidase(GOx),lactate oxidase(LOx)and chloroperoxidase(CPO)are precrosslinked with bovine serum albumin(BSA)to construct nanozymes,which are then biomimetic functionalized with cancer cell membrane to prepare m@BGLC.Benefiting from the biomimetic camouflage with homologous cell membrane,m@BGLC inherit homotypic binding and immune escape abilities,facilitating the tumor targeting accumulation and preferable cell internalization for improved drug delivery efficiency.Subsequently,under the cascade catalysis of nanozymes,m@BGLC consume glucose and lactate for tumor starvation therapy through nutrients deprivation,and meanwhile,the resulting hyprochloric acid(HClO)causes an oxidative damage of cells to synergistically inhibit tumor growth.In vitro and in vivo findings demonstrate a robust tumor eradication effect of m@BGLC without obvious adverse reactions via the targeted combination therapy.Such cascade catalytic nanomedicine may inspire the development of sophisticated strategies for tumor combination therapy under unfavorable tumor microenvironments.展开更多
Polysubstituted chiral γ-butyrolactones are the core structural units of many natural products and high value-added flavors and fragrances used in the food and cosmetic industry. Current enzymatic cascade synthesis o...Polysubstituted chiral γ-butyrolactones are the core structural units of many natural products and high value-added flavors and fragrances used in the food and cosmetic industry. Current enzymatic cascade synthesis of these molecules faces the problems of low enzyme activity and phase separation in batch reaction, resulting in low productivity. Herein, we report a new continuous-flow process to synthesize the optically pure Nicotiana tabacum lactone(3S,4S)-4a and whisky lactone(3R,4S)-4b from α,β-unsaturatedγ-ketoesters. A new ene reductase(ER) from Swingsia samuiensi(Ss ER) and a carbonyl reductase(Ss CR)were engineered by directed evolution to improve their activity and thermostability. The continuous-flow preparative reactions were performed in two 3D microfluidic reactors, generating(3S,4S)-4a(99% ee and87% de) and(3R,4S)-4b(99% ee and 98% de) with space-time yields 3 and 7.4 times higher than those of the batch reactions. The significant enhancement in the productivity of enzyme cascade catalysis brought by cutting-edge continuous microfluidic technology will benefit the general multi-enzyme catalytic systems in the future.展开更多
CO_(2)electrolysis into formate is a promising technology with the potential to simultaneously alleviate energy shortages and global warming.However,the limited stability of the catalysts during long-term electrolysis...CO_(2)electrolysis into formate is a promising technology with the potential to simultaneously alleviate energy shortages and global warming.However,the limited stability of the catalysts during long-term electrolysis hinders their widespread implementation.Herein,we show that a core-shell bimetallic BiAg catalyst with a multifaceted Janus structure at its core can achieve a stability of up to 300 h with a formate faradaic efficiency(FE_(formate))over 90%at−0.75 V vs.RHE(reversible hydrogen electrode)in an H-type cell.Our investigations reveal the important role of the Janus structure on the transfer of electrons,favoring their delocalization across the catalyst and enhancing their mobility.We propose that the compressive strain inclined to grain boundaries within this structure would lower the energy barrier for electrons transfer and promotes the cooperation between Ag and Bi.Indeed,Ag initiates the activation of CO_(2)through a series of cascade reactions and is subsequently hydrogenated on Bi.Additionally,our study suggests that Ag plays a crucial role in stabilizing the catalyst structure after long-term electrolysis.This work highlights a new strategy for tandem CO_(2)electrolysis,providing novel insights for the design of formate formation catalysts.展开更多
Single-atom nanozymes(SAzymes)hold significant potential for tumor catalytic therapy,but their effectiveness is often compromised by low catalytic efficiency within tumor microenvironment.This efficiency is mainly inf...Single-atom nanozymes(SAzymes)hold significant potential for tumor catalytic therapy,but their effectiveness is often compromised by low catalytic efficiency within tumor microenvironment.This efficiency is mainly influenced by key factors including hydrogen peroxide(H_(2)O_(2))availability,acidity,and temperature.Simultaneous optimization of these key factors presents a significant challenge for tumor catalytic therapy.In this study,we developed a comprehensive strategy to refine single-atom catalytic kinetics for enhancing tumor catalytic therapy through dual-enzyme-driven cascade reactions.Iridium(Ir)SAzymes with high catalytic activity and natural enzyme glucose oxidase(GOx)were utilized to construct the cascade reaction system.GOx was loaded by Ir SAzymes due to its large surface area.Then,the dual-enzyme-driven cascade reaction system was modified by cancer cell membranes for improving biocompatibility and achieving tumor homologous targeting ability.GOx catalysis reaction could produce abundant H2O2 and lower the local p H,thereby optimizing key reaction-limiting factors.Additionally,upon laser irradiation,Ir SAzymes could raise local temperature,further enhancing the catalytic efficiency of dual-enzyme system.This comprehensive optimization maximized the performance of Ir SAzymes,significantly improving the efficiency of catalytic therapy.Our findings present a strategy of refining single-atom catalytic kinetics for tumor homologous-targeted catalytic therapy.展开更多
The electrocatalytic selective oxidation of alcohol for direct heterocyclic ring compound production under ambient conditions is highly desirable but greatly challenging,due to the fast oxidation kinetics of aldehyde ...The electrocatalytic selective oxidation of alcohol for direct heterocyclic ring compound production under ambient conditions is highly desirable but greatly challenging,due to the fast oxidation kinetics of aldehyde intermediate species during electrocatalysis.Here,for the first time,an electro-acidic catalytic cascade reaction strategy has been developed for the efficient and selective conversion from ethylene glycol to 1,4-Dioxane-2,5-diol under ambient conditions on synthesized CeO_(2)-e-Pd/CP electrocatalyst,which features a significantly high faraday efficiency of 83.6%.The CeO_(2)in the electrocatalyst induces the downshift of the d-band center of Pd,which favors the fast desorption of glycolaldehyde from the electrocatalyst with ease into the acidic electrolyte,facilitating its subsequent condensation into 1,4-Dioxane-2,5-diol through C-O coupling while preventing the overoxidation of the glycolaldehyde intermediate into carboxylic acids.This work provides a novel strategy and insight into the reaction design for the synthesis of heterocyclic ring productions from simple molecules.展开更多
The commercialization of lithium-sulfur(Li-S)batteries has been struggling due to the uncontrollable shuttle effect and slow polysulfides redox kinetics.Single atom alloys(SAAs)with the advantages of single-atom and n...The commercialization of lithium-sulfur(Li-S)batteries has been struggling due to the uncontrollable shuttle effect and slow polysulfides redox kinetics.Single atom alloys(SAAs)with the advantages of single-atom and nanoparticle catalysts are still rarely studied in the field of Li-S batteries.Herein,a NiCo_(SAA)was supported on MXene(NiCo_(SAA)-MXene),which served as the cascade electrocatalyst for improving the Li^(+)desolvation and polysulfides conversion kinetics.In this design,the special structure of the single atom alloy can fully inhibit the mutual stacking of MXene and achieve good stability,while the MXene nanosheet serves as support to enable the uniform dispersion of single atom alloy with ultra-small particle size,facilitating maximum atom utilization.Moreover,the electron cloud of Co was redistributed with the assistance of Ni,resulting in an enhanced electrocatalytic performance,as confirmed by theoretical calculations.At the cascade catalysis of NiCo_(SAA)-MXene,more free Li^(+)was released,and the diffusion of Li^(+)was enhanced to participate in the polysulfides redox reaction,effectively inhibiting the shuttle effect of polysulfides,as proved by in-situ/ex-situ Raman and electrochemical characterization.As a result,the Li-S battery with NiCo_(SAA)-MXene modified separator achieved a reversible capacity of 992 mAh·g^(-1)at 0.2 C after 100 cycles and a superior rate capability of 746 mAh·g^(-1)at 4 C.At a high sulfur loading of 4.7 mg·cm^(-2),the Li-S battery also maintains an excellent cycling stability(100 cycles,3.1 mAh·cm^(-2)),demonstrating significant promise for commercial applications.展开更多
Effective intervention in glycolytic metabolism is a promising way to inhibit tumor malignant invasion.However,the inherent hypoxia environment and unitary regulating model subsequently compromise its therapeutic effi...Effective intervention in glycolytic metabolism is a promising way to inhibit tumor malignant invasion.However,the inherent hypoxia environment and unitary regulating model subsequently compromise its therapeutic efficacy.Herein,a facile way to design an automatic metabolism modulator(auto-MMOD)is developed by loading glucose oxidase(GOx)and DNA-templated silver nanoclusters(DNA-AgNCs)into a pH-responsive zeolitic imidazolate frameworks-8(ZIF-8)nanocarrier,which can activate a cascaded metal ion-killing effect during GOx-regulated glycolysis metabolism.When the acidic lysosome microenvironment induces ZIF-8 decomposition,the released GOx can effectively consume glucose and generate H_(2)O_(2),thus inhibiting Adenosine Triphosphate synthesis and accelerating tumor starvation.Moreover,the released Ag+in response to H_(2)O_(2) can disturb bioenergy metabolism to inhibit tumor proliferation,which further enhances the tumor-killing effect in hypoxic microenvironments.This study achieves effective tumor suppression in vitro and in vivo by integrating ion therapy into glycolysis intervention,which establish a promising strategy for nano-theranostics.展开更多
Highly evolved multi-enzyme cascade catalytic reactions in organisms facilitate rapid transfer of substrates and efficient conversion of intermediates in the catalytic unit,thus rationalizing their efficient biocataly...Highly evolved multi-enzyme cascade catalytic reactions in organisms facilitate rapid transfer of substrates and efficient conversion of intermediates in the catalytic unit,thus rationalizing their efficient biocatalysis.In this study,pore-ordered mesoporous single-atom(Fe)nitrogen-doped carbon nanoreactors(Mp-Fe-CN)were designed,in which a reasonable pore size was designed as a natural enzyme trap coupled to a simulated enzyme center.A polarity-mediated strategy was developed to obtain atomically dispersed nanoporous substrates,with the finding that polarity-guided engineering of the nitrogen-ligand environment and vacancy cluster defects clearly affects nanoporous activity,accompanied by appreciable mesoporous pore size elevation.The active center and distal N atom coordination of Fe-N_(4) affect the catalytic process of the nanozyme exposed by density functional theory(DFT),determining the contribution of hybridized orbitals to electron transfer and the decisive step.A cascade nanoreactor-based domain-limited sarcosine oxidase developed for non-invasive monitoring of sarcosine levels in urine for evaluation of potential prostate carcinogenesis as a proof of concept.Based on the design of surface mesoporous channels of nanocatalytic units,a bridge was built for the interaction between nanozymes and natural enzymes to achieve cascade nanocatalysis of natural enzymatic products.展开更多
基金financial support of Guangdong Basic and Applied Basic Research Foundation(No.2022B1515020095)National Natural Science Foundation of China(No.52073140)。
文摘Deprivation of glucose and lactate provides an effective pathway to terminate the nutrients supplement for tumor growth.In this work,biomimetic nanozymes called m@BGLC are constructed for catalytic tumor inhibition through nutrients deprivation and oxidative damage induction.Concretely,the catalytic enzymes of glucose oxidase(GOx),lactate oxidase(LOx)and chloroperoxidase(CPO)are precrosslinked with bovine serum albumin(BSA)to construct nanozymes,which are then biomimetic functionalized with cancer cell membrane to prepare m@BGLC.Benefiting from the biomimetic camouflage with homologous cell membrane,m@BGLC inherit homotypic binding and immune escape abilities,facilitating the tumor targeting accumulation and preferable cell internalization for improved drug delivery efficiency.Subsequently,under the cascade catalysis of nanozymes,m@BGLC consume glucose and lactate for tumor starvation therapy through nutrients deprivation,and meanwhile,the resulting hyprochloric acid(HClO)causes an oxidative damage of cells to synergistically inhibit tumor growth.In vitro and in vivo findings demonstrate a robust tumor eradication effect of m@BGLC without obvious adverse reactions via the targeted combination therapy.Such cascade catalytic nanomedicine may inspire the development of sophisticated strategies for tumor combination therapy under unfavorable tumor microenvironments.
基金financially sponsored by the National Key Research and Development Program of China (No.2021YFC2102804)the National Natural Science Foundation of China(No.22078096)。
文摘Polysubstituted chiral γ-butyrolactones are the core structural units of many natural products and high value-added flavors and fragrances used in the food and cosmetic industry. Current enzymatic cascade synthesis of these molecules faces the problems of low enzyme activity and phase separation in batch reaction, resulting in low productivity. Herein, we report a new continuous-flow process to synthesize the optically pure Nicotiana tabacum lactone(3S,4S)-4a and whisky lactone(3R,4S)-4b from α,β-unsaturatedγ-ketoesters. A new ene reductase(ER) from Swingsia samuiensi(Ss ER) and a carbonyl reductase(Ss CR)were engineered by directed evolution to improve their activity and thermostability. The continuous-flow preparative reactions were performed in two 3D microfluidic reactors, generating(3S,4S)-4a(99% ee and87% de) and(3R,4S)-4b(99% ee and 98% de) with space-time yields 3 and 7.4 times higher than those of the batch reactions. The significant enhancement in the productivity of enzyme cascade catalysis brought by cutting-edge continuous microfluidic technology will benefit the general multi-enzyme catalytic systems in the future.
基金the Max Planck Centre for Fundamental Heterogeneous Catalysis(FUNCAT)for financial supportThe authors acknowledge funding from the National Natural Science Foundation of China(No.22002131)China Postdoctoral Science Foundation(No.2020M671963)。
文摘CO_(2)electrolysis into formate is a promising technology with the potential to simultaneously alleviate energy shortages and global warming.However,the limited stability of the catalysts during long-term electrolysis hinders their widespread implementation.Herein,we show that a core-shell bimetallic BiAg catalyst with a multifaceted Janus structure at its core can achieve a stability of up to 300 h with a formate faradaic efficiency(FE_(formate))over 90%at−0.75 V vs.RHE(reversible hydrogen electrode)in an H-type cell.Our investigations reveal the important role of the Janus structure on the transfer of electrons,favoring their delocalization across the catalyst and enhancing their mobility.We propose that the compressive strain inclined to grain boundaries within this structure would lower the energy barrier for electrons transfer and promotes the cooperation between Ag and Bi.Indeed,Ag initiates the activation of CO_(2)through a series of cascade reactions and is subsequently hydrogenated on Bi.Additionally,our study suggests that Ag plays a crucial role in stabilizing the catalyst structure after long-term electrolysis.This work highlights a new strategy for tandem CO_(2)electrolysis,providing novel insights for the design of formate formation catalysts.
基金financially supported by National Natural Science Foundation of China(U23A2097,82372116,22474079,22104094,82302362)Shenzhen Medical Research Fund(B2302047)+3 种基金Basic Research Program of Shenzhen(KQTD20190929172538530,JCYJ20220818095806014,JCYJ20240813142810014)Natural Science Foundation of Guangdong Province(2024A1515012677)Research Team Cultivation Program of Shenzhen University(2023QNT017,2023QNT019)Shenzhen University 2035 Program for Excellent Research(2024C004)。
文摘Single-atom nanozymes(SAzymes)hold significant potential for tumor catalytic therapy,but their effectiveness is often compromised by low catalytic efficiency within tumor microenvironment.This efficiency is mainly influenced by key factors including hydrogen peroxide(H_(2)O_(2))availability,acidity,and temperature.Simultaneous optimization of these key factors presents a significant challenge for tumor catalytic therapy.In this study,we developed a comprehensive strategy to refine single-atom catalytic kinetics for enhancing tumor catalytic therapy through dual-enzyme-driven cascade reactions.Iridium(Ir)SAzymes with high catalytic activity and natural enzyme glucose oxidase(GOx)were utilized to construct the cascade reaction system.GOx was loaded by Ir SAzymes due to its large surface area.Then,the dual-enzyme-driven cascade reaction system was modified by cancer cell membranes for improving biocompatibility and achieving tumor homologous targeting ability.GOx catalysis reaction could produce abundant H2O2 and lower the local p H,thereby optimizing key reaction-limiting factors.Additionally,upon laser irradiation,Ir SAzymes could raise local temperature,further enhancing the catalytic efficiency of dual-enzyme system.This comprehensive optimization maximized the performance of Ir SAzymes,significantly improving the efficiency of catalytic therapy.Our findings present a strategy of refining single-atom catalytic kinetics for tumor homologous-targeted catalytic therapy.
基金supported by the National Key R&D Program of China(grant no.2022YFB4002700)the Shanghai Science and Technology Committee Rising-Star Program(grant no.22QA1403400)the Natural Science Foundation of Shanghai(grant no.21ZR1418700).
文摘The electrocatalytic selective oxidation of alcohol for direct heterocyclic ring compound production under ambient conditions is highly desirable but greatly challenging,due to the fast oxidation kinetics of aldehyde intermediate species during electrocatalysis.Here,for the first time,an electro-acidic catalytic cascade reaction strategy has been developed for the efficient and selective conversion from ethylene glycol to 1,4-Dioxane-2,5-diol under ambient conditions on synthesized CeO_(2)-e-Pd/CP electrocatalyst,which features a significantly high faraday efficiency of 83.6%.The CeO_(2)in the electrocatalyst induces the downshift of the d-band center of Pd,which favors the fast desorption of glycolaldehyde from the electrocatalyst with ease into the acidic electrolyte,facilitating its subsequent condensation into 1,4-Dioxane-2,5-diol through C-O coupling while preventing the overoxidation of the glycolaldehyde intermediate into carboxylic acids.This work provides a novel strategy and insight into the reaction design for the synthesis of heterocyclic ring productions from simple molecules.
基金supported by the National Natural Science Foundation of China(Nos.U21A2060,22178116,and 21978097)Natural Science Foundation of Shanghai(No.22ZR1417400)+3 种基金the Fundamental Research Funds for the Central Universities(No.JKD01231701)China Postdoctoral Science Foundation(No.2023M731084)Shanghai Sailing Program of China(No.23YF1408900)Fundamental Research Funds for the Central Universities(Nos.222201817001,50321041918013,and JKA01221601).
文摘The commercialization of lithium-sulfur(Li-S)batteries has been struggling due to the uncontrollable shuttle effect and slow polysulfides redox kinetics.Single atom alloys(SAAs)with the advantages of single-atom and nanoparticle catalysts are still rarely studied in the field of Li-S batteries.Herein,a NiCo_(SAA)was supported on MXene(NiCo_(SAA)-MXene),which served as the cascade electrocatalyst for improving the Li^(+)desolvation and polysulfides conversion kinetics.In this design,the special structure of the single atom alloy can fully inhibit the mutual stacking of MXene and achieve good stability,while the MXene nanosheet serves as support to enable the uniform dispersion of single atom alloy with ultra-small particle size,facilitating maximum atom utilization.Moreover,the electron cloud of Co was redistributed with the assistance of Ni,resulting in an enhanced electrocatalytic performance,as confirmed by theoretical calculations.At the cascade catalysis of NiCo_(SAA)-MXene,more free Li^(+)was released,and the diffusion of Li^(+)was enhanced to participate in the polysulfides redox reaction,effectively inhibiting the shuttle effect of polysulfides,as proved by in-situ/ex-situ Raman and electrochemical characterization.As a result,the Li-S battery with NiCo_(SAA)-MXene modified separator achieved a reversible capacity of 992 mAh·g^(-1)at 0.2 C after 100 cycles and a superior rate capability of 746 mAh·g^(-1)at 4 C.At a high sulfur loading of 4.7 mg·cm^(-2),the Li-S battery also maintains an excellent cycling stability(100 cycles,3.1 mAh·cm^(-2)),demonstrating significant promise for commercial applications.
基金National Natural Science Foundation of China,Grant/Award Numbers:22474067,22076087Special Funds of the Taishan Scholar Program of Shandong Province,Grant/Award Numbers:tstp20230623,tsqn20231217+3 种基金Natural Science Foundation of Shandong Province,Grant/Award Number:ZR2023QB104Natural Science Foundation of Qingdao,Grant/Award Number:23-2-1-11-zyyd-jchNational Key R&D Program of China-"Intergovernmental International Cooperation on Science and Technology Innovation"Key Special Project,Grant/Award Number:2024YFE0104100‘Medicine Plus'Joint Research Program of Qingdao University,Grant/Award Number:YX2024201。
文摘Effective intervention in glycolytic metabolism is a promising way to inhibit tumor malignant invasion.However,the inherent hypoxia environment and unitary regulating model subsequently compromise its therapeutic efficacy.Herein,a facile way to design an automatic metabolism modulator(auto-MMOD)is developed by loading glucose oxidase(GOx)and DNA-templated silver nanoclusters(DNA-AgNCs)into a pH-responsive zeolitic imidazolate frameworks-8(ZIF-8)nanocarrier,which can activate a cascaded metal ion-killing effect during GOx-regulated glycolysis metabolism.When the acidic lysosome microenvironment induces ZIF-8 decomposition,the released GOx can effectively consume glucose and generate H_(2)O_(2),thus inhibiting Adenosine Triphosphate synthesis and accelerating tumor starvation.Moreover,the released Ag+in response to H_(2)O_(2) can disturb bioenergy metabolism to inhibit tumor proliferation,which further enhances the tumor-killing effect in hypoxic microenvironments.This study achieves effective tumor suppression in vitro and in vivo by integrating ion therapy into glycolysis intervention,which establish a promising strategy for nano-theranostics.
基金supported by the National Natural Science Foundation of China(Nos.22274022,21874022 and 21675029).
文摘Highly evolved multi-enzyme cascade catalytic reactions in organisms facilitate rapid transfer of substrates and efficient conversion of intermediates in the catalytic unit,thus rationalizing their efficient biocatalysis.In this study,pore-ordered mesoporous single-atom(Fe)nitrogen-doped carbon nanoreactors(Mp-Fe-CN)were designed,in which a reasonable pore size was designed as a natural enzyme trap coupled to a simulated enzyme center.A polarity-mediated strategy was developed to obtain atomically dispersed nanoporous substrates,with the finding that polarity-guided engineering of the nitrogen-ligand environment and vacancy cluster defects clearly affects nanoporous activity,accompanied by appreciable mesoporous pore size elevation.The active center and distal N atom coordination of Fe-N_(4) affect the catalytic process of the nanozyme exposed by density functional theory(DFT),determining the contribution of hybridized orbitals to electron transfer and the decisive step.A cascade nanoreactor-based domain-limited sarcosine oxidase developed for non-invasive monitoring of sarcosine levels in urine for evaluation of potential prostate carcinogenesis as a proof of concept.Based on the design of surface mesoporous channels of nanocatalytic units,a bridge was built for the interaction between nanozymes and natural enzymes to achieve cascade nanocatalysis of natural enzymatic products.
