Membrane structures play a crucial role in biological systems,not only serving as a barrier between cells/organelles and the external microenvironment but also playing key roles in important biological processes such ...Membrane structures play a crucial role in biological systems,not only serving as a barrier between cells/organelles and the external microenvironment but also playing key roles in important biological processes such as material exchange,signal transduction,and cell proliferation.With the advancement of related research,membranetargeting strategies have gradually been a focus in modern cancer therapy and antimicrobial studies.Polymer materials show great promise in membrane-targeted therapy due to their excellent biocompatibility,tunability,and functionalization potential.Presented in this review are design strategies for polymer materials targeting cell and organelle membranes.Initially,we introduce the functions and characteristics of tumor cell membranes,organelle membranes,and bacterial cell walls,whose unique physicochemical properties offer potential pathways for targeted therapy.Next,we focus on various strategies for designing polymer materials with membrane targeting features.For instance,by adjusting the charge density and hydrophilicity/hydrophobicity of polymer chains,cationic polymers(e.g.,polyethylenimine and polyamidoamine dendrimers)can leverage electrostatic interactions to disrupt the integrity of the cell membrane,leading to pore formation or structural disruption,which facilitates efficient cytosolic delivery.Thirdly,functionalized polymers can specifically recognize target membranes,thereby reducing side effects.Studies have demonstrated that modified polymers not only facilitate targeted delivery to specific organs but also enhance cellular uptake efficiency by up to 10 times.Finally,we discuss existing challenges and future directions of polymer materials for membrane-targeted therapeutics,aiming to provide insight for advancing membrane-targeted polymers and improving existing treatment strategies for more precise disease management.展开更多
Peptides exert important biological functions but their application is hindered by their susceptibility to proteolysis and poor stability in vivo.Thus,functional peptide mimics have drawn a great deal of attention to ...Peptides exert important biological functions but their application is hindered by their susceptibility to proteolysis and poor stability in vivo.Thus,functional peptide mimics have drawn a great deal of attention to address this challenge.Poly(2-oxazoline)s,a class of biocompatible and proteolysis-resistant polymer,can work as host defense peptide mimics without following the general membrane-targeting mechanism as shown in our previous work.This observation encouraged us to figure out if poly(2-oxazoline)s are special and break the general membrane-targeting mechanism of host defense peptides and their mimics.In this study,we aimed at the connection between structure and antibacterial mechanism of poly(2-oxazoline)s.A new γ-aminobutyric acid(GABA)-pendent poly(2-oxazoline)was synthesized and investigated to compare with glycine-pendent poly(2-oxazoline)in our previous study,with the former polymer has two extra CH2 groups in the sidechain to increase the hydrophobicity and amphiphilicity.Membrane depolarization assay suggested that incorporating two more CH2 groups into the sidechain of poly(2-oxazoline)resulted in a mechanism switch from DNA-targeting to membrane-targeting,which was supported by the slow time-kill kinetics and slightly distorted and sunken membrane morphology.Besides,GABA-pendent poly(2-oxazoline)showed potent activity against methicillin-resistant S.aureus and low hemolysis on human red blood cells.Moreover,repeated use of the antimicrobial poly(2-oxazoline)did not stimulate bacteria to obtain resistance,which was an obvious advantage of membrane-targeting antimicrobial agents.展开更多
An amphiphilic AIE photosensitizer has been successfully developed,which allows for easily inserting into the bacterial membranes.Binding experiments with phospholipid preliminary demonstrates its membrane specificity...An amphiphilic AIE photosensitizer has been successfully developed,which allows for easily inserting into the bacterial membranes.Binding experiments with phospholipid preliminary demonstrates its membrane specificity.As expected,it is proved to possess a broad-spectrum bacterial staining performance and photodynamic antibacterial activity toward S.aureus and E.coli.展开更多
基金supported by National Natural Science Foundation of China(52222306,22075212,22335005 and 22305177)international scientific collaboration fund of Science and Technology Commission of Shanghai Municipality(23520710900)+3 种基金Innovation Program of Shanghai Municipal Education Commission(2023ZKZD28)the fellowship of China Postdoctoral Science Foundation(2022M720107,GZB20230517,2024T170668)Shanghai“Super Postdoc”Incentive Plan(2022568)Shanghai Rising-Star Program(Sailing,23YF1433000).
文摘Membrane structures play a crucial role in biological systems,not only serving as a barrier between cells/organelles and the external microenvironment but also playing key roles in important biological processes such as material exchange,signal transduction,and cell proliferation.With the advancement of related research,membranetargeting strategies have gradually been a focus in modern cancer therapy and antimicrobial studies.Polymer materials show great promise in membrane-targeted therapy due to their excellent biocompatibility,tunability,and functionalization potential.Presented in this review are design strategies for polymer materials targeting cell and organelle membranes.Initially,we introduce the functions and characteristics of tumor cell membranes,organelle membranes,and bacterial cell walls,whose unique physicochemical properties offer potential pathways for targeted therapy.Next,we focus on various strategies for designing polymer materials with membrane targeting features.For instance,by adjusting the charge density and hydrophilicity/hydrophobicity of polymer chains,cationic polymers(e.g.,polyethylenimine and polyamidoamine dendrimers)can leverage electrostatic interactions to disrupt the integrity of the cell membrane,leading to pore formation or structural disruption,which facilitates efficient cytosolic delivery.Thirdly,functionalized polymers can specifically recognize target membranes,thereby reducing side effects.Studies have demonstrated that modified polymers not only facilitate targeted delivery to specific organs but also enhance cellular uptake efficiency by up to 10 times.Finally,we discuss existing challenges and future directions of polymer materials for membrane-targeted therapeutics,aiming to provide insight for advancing membrane-targeted polymers and improving existing treatment strategies for more precise disease management.
基金financially supported by the Natural Science Foundation of Shanghai(18ZR1410300)the National Natural Science Foundation of China(No.21861162010,21774031)+2 种基金the National Key Research and Development Program of China(No.2016YFC1100401)the Research Program of State Key Laboratory of Bioreactor Engineeringthe Fundamental Research Funds for the Central Universities(No.22221818014,50321041917001)。
文摘Peptides exert important biological functions but their application is hindered by their susceptibility to proteolysis and poor stability in vivo.Thus,functional peptide mimics have drawn a great deal of attention to address this challenge.Poly(2-oxazoline)s,a class of biocompatible and proteolysis-resistant polymer,can work as host defense peptide mimics without following the general membrane-targeting mechanism as shown in our previous work.This observation encouraged us to figure out if poly(2-oxazoline)s are special and break the general membrane-targeting mechanism of host defense peptides and their mimics.In this study,we aimed at the connection between structure and antibacterial mechanism of poly(2-oxazoline)s.A new γ-aminobutyric acid(GABA)-pendent poly(2-oxazoline)was synthesized and investigated to compare with glycine-pendent poly(2-oxazoline)in our previous study,with the former polymer has two extra CH2 groups in the sidechain to increase the hydrophobicity and amphiphilicity.Membrane depolarization assay suggested that incorporating two more CH2 groups into the sidechain of poly(2-oxazoline)resulted in a mechanism switch from DNA-targeting to membrane-targeting,which was supported by the slow time-kill kinetics and slightly distorted and sunken membrane morphology.Besides,GABA-pendent poly(2-oxazoline)showed potent activity against methicillin-resistant S.aureus and low hemolysis on human red blood cells.Moreover,repeated use of the antimicrobial poly(2-oxazoline)did not stimulate bacteria to obtain resistance,which was an obvious advantage of membrane-targeting antimicrobial agents.
基金financial support from Natural Science Foundation of Henan Province(No.222300420501)the Key Scientific and Technological Project of Henan province(No.212102210549)+1 种基金the Key Scientific Research Project of Higher Education of Henan Province(No.22A430007)National College Students Innovation and Entrepreneurship Training Program(No.202210482028)。
文摘An amphiphilic AIE photosensitizer has been successfully developed,which allows for easily inserting into the bacterial membranes.Binding experiments with phospholipid preliminary demonstrates its membrane specificity.As expected,it is proved to possess a broad-spectrum bacterial staining performance and photodynamic antibacterial activity toward S.aureus and E.coli.
