Lipid peroxidation(LPO),the process of membrane lipid oxidation,is a potential new form of cell death for cancer treatment.However,the radical chain reaction involved in LPO is comprised of the initiation,propagation(...Lipid peroxidation(LPO),the process of membrane lipid oxidation,is a potential new form of cell death for cancer treatment.However,the radical chain reaction involved in LPO is comprised of the initiation,propagation(the slowest step),and termination stages,limiting its effectiveness in vivo.To address this limitation,we introduce the radical chain transfer reaction into the LPO process to target the propagation step and overcome the sluggish rate of lipid peroxidation,thereby promoting endogenous lipid peroxidation and enhancing therapeutic outcomes.Firstly,radical chain transfer agent(CTA-1)/Fe nanoparticles(CTA-Fe NPs-1)was synthesized.Notably,CTA-1 convert low activity peroxyl radicals(ROO·)into high activity alkoxyl radicals(RO·),creating the cycle of free radical oxidation and increasing the propagation of lipid peroxidation.Additionally,CTA-1/Fe ions enhance reactive oxygen species(ROS)generation,consume glutathione(GSH),and thereby inactivate GPX-4,promoting the initiation stage and reducing termination of free radical reaction.CTA-Fe NPs-1 induce a higher level of peroxidation of polyunsaturated fatty acids in lipid membranes,leading to highly effective treatment in cancer cells.In addition,CTA-Fe NPs-1 could be enriched in tumors inducing potent tumor inhibition and exhibit activatable T1-MRI contrast of magnetic resonance imaging(MRI).In summary,CTA-Fe NPs-1 can enhance intracellular lipid peroxidation by accelerating initiation,propagation,and inhibiting termination step,promoting the cycle of free radical reaction,resulting in effective anticancer outcomes in tumor-bearing mice.展开更多
Stereoblock polypropyienes bearing isotactic,atactic,and syndictactic polypropylene segments were successfully prepared by dry methylaluminoxane activated binary catalysts system,Ph2CFluCpZrCl2 and {Me2Si(2,5-Me2-3-(2...Stereoblock polypropyienes bearing isotactic,atactic,and syndictactic polypropylene segments were successfully prepared by dry methylaluminoxane activated binary catalysts system,Ph2CFluCpZrCl2 and {Me2Si(2,5-Me2-3-(2-MePh)-cyclopento[2,3-b]thiophen-6-yl)2}ZCl2,in the presence of iBu3Al as a chain shutting agent.by studying the catalyst activity,chain transfer efficiency,and reversility of chain transfer reaction of each catalyst system,as well as the molecular weight and polydispersity of the resulting polymers,the allyl exchange reactions between the zirconium catalyst and different main-group metal alky were estimated,respectvely.Based on the optimized react condition,the chain shuttling polymerization was conducted by binary catalyst system in the presence of iBu3Al under both atmospheric and high pressure.Resultant polymers were identified as stereoblock polypropylenes according to microstructure and physical properties analyses by 13C{1H}-NMR,DsC,and GPC.展开更多
基金supported by the National Natural Science Foundation of China(U21A20287 and 22234003)Shenzhen Science and Technology Program(JCYJ20210324140205013)。
文摘Lipid peroxidation(LPO),the process of membrane lipid oxidation,is a potential new form of cell death for cancer treatment.However,the radical chain reaction involved in LPO is comprised of the initiation,propagation(the slowest step),and termination stages,limiting its effectiveness in vivo.To address this limitation,we introduce the radical chain transfer reaction into the LPO process to target the propagation step and overcome the sluggish rate of lipid peroxidation,thereby promoting endogenous lipid peroxidation and enhancing therapeutic outcomes.Firstly,radical chain transfer agent(CTA-1)/Fe nanoparticles(CTA-Fe NPs-1)was synthesized.Notably,CTA-1 convert low activity peroxyl radicals(ROO·)into high activity alkoxyl radicals(RO·),creating the cycle of free radical oxidation and increasing the propagation of lipid peroxidation.Additionally,CTA-1/Fe ions enhance reactive oxygen species(ROS)generation,consume glutathione(GSH),and thereby inactivate GPX-4,promoting the initiation stage and reducing termination of free radical reaction.CTA-Fe NPs-1 induce a higher level of peroxidation of polyunsaturated fatty acids in lipid membranes,leading to highly effective treatment in cancer cells.In addition,CTA-Fe NPs-1 could be enriched in tumors inducing potent tumor inhibition and exhibit activatable T1-MRI contrast of magnetic resonance imaging(MRI).In summary,CTA-Fe NPs-1 can enhance intracellular lipid peroxidation by accelerating initiation,propagation,and inhibiting termination step,promoting the cycle of free radical reaction,resulting in effective anticancer outcomes in tumor-bearing mice.
基金the National Natural Science Foundation of China(No.21574097).
文摘Stereoblock polypropyienes bearing isotactic,atactic,and syndictactic polypropylene segments were successfully prepared by dry methylaluminoxane activated binary catalysts system,Ph2CFluCpZrCl2 and {Me2Si(2,5-Me2-3-(2-MePh)-cyclopento[2,3-b]thiophen-6-yl)2}ZCl2,in the presence of iBu3Al as a chain shutting agent.by studying the catalyst activity,chain transfer efficiency,and reversility of chain transfer reaction of each catalyst system,as well as the molecular weight and polydispersity of the resulting polymers,the allyl exchange reactions between the zirconium catalyst and different main-group metal alky were estimated,respectvely.Based on the optimized react condition,the chain shuttling polymerization was conducted by binary catalyst system in the presence of iBu3Al under both atmospheric and high pressure.Resultant polymers were identified as stereoblock polypropylenes according to microstructure and physical properties analyses by 13C{1H}-NMR,DsC,and GPC.
