Insufficient endogenous H_(2)O_(2)for generation of hydroxyl radicals(°OH)has strikingly compromised anti-tumor benefits of ferroptosis.Herein,we develop a H_(2)O_(2)self-supplying nanoparticle based on a pH-resp...Insufficient endogenous H_(2)O_(2)for generation of hydroxyl radicals(°OH)has strikingly compromised anti-tumor benefits of ferroptosis.Herein,we develop a H_(2)O_(2)self-supplying nanoparticle based on a pH-responsive lipopeptide C_(18)-pHis_(10).Inspired by the coordinate pattern of hemoglobin binding heme,Fe^(2+)and tetrakis(4-carboxyphenyl)porphyrin(TCPP)were delicately encapsulated by formation of coordination compounds with His.Ascorbgyl palmitate(AscP)was also incorporated into the nanoparticles for gener-ation of H_(2)O_(2)by reduction^(1)0_(2)produced from TCPP,meanwhile prevented Fe^(2+)from being oxidized.The protonation of pHis in acidic endo-lysosome induced the breakage of Fe^(2+)/His/TCPP coordinate in-teractions,leading to accelerated release of payloads and the following escape to cytoplasm.Upon laser irradiation,TCPP produces excessive^(1)0_(2)followed by conversion to H_(2)O_(2)in the presence of AscP,which is further catalyzed to lethal OH by Fe^(2+)via Fenton reaction.The self-supplying H_(2)O_(2)was found to re-sult significantly higher accumulation of lipid peroxides and more effective tumor inhibition.Overall,this work sheds new a light on H_(2)O_(2)self-supplying strategy to enhance ferroptosis by taking advantage of^(1)0_(2)generated by photodynamic therapy(PDT).展开更多
A self-assembled Pd_4L_2 cage is employed as a water-soluble molecular flask for the synthesis of functionalized coumarins from a series of salicylaldehyde derivatives and cyanoacetates/malononitrile. The catalytic re...A self-assembled Pd_4L_2 cage is employed as a water-soluble molecular flask for the synthesis of functionalized coumarins from a series of salicylaldehyde derivatives and cyanoacetates/malononitrile. The catalytic reaction features mild aqueous conditions and broad substrate scope. Crystal structures of the host-vip complexes for two substrates and one analogous intermediate have been obtained, shedding light on the supramolecular reaction mechanism. Michaelis-Menten kinetic studies were performed in one typical case, revealing that the rate of product formation has been enhanced by over 23-fold in contrast to the background reaction without cage. Moreover, the same reaction catalyzed by a smaller Pd_6L_4 cage gives a mixture of products and much lower yields, suggesting that fine-tuning on the size and symmetry of the cages' cavity is crucial for their applications in supramolecular catalysis.展开更多
基金funding of National Natural Science Foundation of China(Nos.82304426 and 81573372)Postdoctoral Fellowship Program of CPSF(No.GZC20231730)Career Development Support Plan for Young and Middle-aged Teachers in Shenyang Pharmaceutical University(No.ZQN2014A03).
文摘Insufficient endogenous H_(2)O_(2)for generation of hydroxyl radicals(°OH)has strikingly compromised anti-tumor benefits of ferroptosis.Herein,we develop a H_(2)O_(2)self-supplying nanoparticle based on a pH-responsive lipopeptide C_(18)-pHis_(10).Inspired by the coordinate pattern of hemoglobin binding heme,Fe^(2+)and tetrakis(4-carboxyphenyl)porphyrin(TCPP)were delicately encapsulated by formation of coordination compounds with His.Ascorbgyl palmitate(AscP)was also incorporated into the nanoparticles for gener-ation of H_(2)O_(2)by reduction^(1)0_(2)produced from TCPP,meanwhile prevented Fe^(2+)from being oxidized.The protonation of pHis in acidic endo-lysosome induced the breakage of Fe^(2+)/His/TCPP coordinate in-teractions,leading to accelerated release of payloads and the following escape to cytoplasm.Upon laser irradiation,TCPP produces excessive^(1)0_(2)followed by conversion to H_(2)O_(2)in the presence of AscP,which is further catalyzed to lethal OH by Fe^(2+)via Fenton reaction.The self-supplying H_(2)O_(2)was found to re-sult significantly higher accumulation of lipid peroxides and more effective tumor inhibition.Overall,this work sheds new a light on H_(2)O_(2)self-supplying strategy to enhance ferroptosis by taking advantage of^(1)0_(2)generated by photodynamic therapy(PDT).
基金supported by the National Natural Science Foundation of China (21825107, 21601183, 21801241, 21571090)Natural Science Foundation of Fujian Province (2016J05051, 2017J05037)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB20000000)
文摘A self-assembled Pd_4L_2 cage is employed as a water-soluble molecular flask for the synthesis of functionalized coumarins from a series of salicylaldehyde derivatives and cyanoacetates/malononitrile. The catalytic reaction features mild aqueous conditions and broad substrate scope. Crystal structures of the host-vip complexes for two substrates and one analogous intermediate have been obtained, shedding light on the supramolecular reaction mechanism. Michaelis-Menten kinetic studies were performed in one typical case, revealing that the rate of product formation has been enhanced by over 23-fold in contrast to the background reaction without cage. Moreover, the same reaction catalyzed by a smaller Pd_6L_4 cage gives a mixture of products and much lower yields, suggesting that fine-tuning on the size and symmetry of the cages' cavity is crucial for their applications in supramolecular catalysis.
