Supported cell membrane coatings meet many requirements set to bioactive nanocarriers and materials,provided sidedness and fluidity of the natural membrane are maintained upon coating.However,the properties of a suppo...Supported cell membrane coatings meet many requirements set to bioactive nanocarriers and materials,provided sidedness and fluidity of the natural membrane are maintained upon coating.However,the properties of a support-surface responsible for maintaining correct sidedness and fluidity are unknown.Here,we briefly review the properties of natural membranes and membrane-isolation methods,with focus on the asymmetric distribution of functional groups in natural membranes(sidedness)and the ability of molecules to float across a membrane to form functional domains(fluidity).This review concludes that hydrophilic sugar-residues of glycoproteins in the outer-leaflet of cell membranes direct the more hydrophobic inner-leaflet towards a support-surface to create a correctly-sided membrane coating,regardless of electrostatic double-layer interactions.On positively-charged support-surfaces however,strong,electrostatic double-layer attraction of negatively-charged membranes can impede homogeneous coating.In correctly-sided membrane coatings,fluidity is maintained regardless of whether the surface carries a positive or negative charge.However,membranes are frozen on positively-charged,highly-curved,small nanoparticles and localized nanoscopic structures on a support-surface.This leaves an unsupported membrane coating in between nanostructures on planar support-surfaces that is in dual-sided contact with its aqueous environment,yielding enhanced fluidity in membrane coatings on nanostructured,planar support-surfaces as compared with smooth ones.展开更多
Increasing occurrence of intrinsically antimicrobial-resistant,human pathogens and the protective biofilm-mode in which they grow,dictates a need for the alternative control of infectious biofilms.Biofilm bacteria uti...Increasing occurrence of intrinsically antimicrobial-resistant,human pathogens and the protective biofilm-mode in which they grow,dictates a need for the alternative control of infectious biofilms.Biofilm bacteria utilize dispersal mechanisms to detach parts of a biofilm as part of the biofilm life-cycle during times of nutrient scarcity or overpopulation.We here identify recent advances and future challenges in the development of dispersants as a new infection-control strategy.Deoxyribonuclease(DNase)and other extracellular enzymes can disrupt the extracellular matrix of a biofilm to cause dispersal.Also,a variety of small molecules,reactive oxygen species,nitric oxide releasing compounds,peptides and molecules regulating signaling pathways in biofilms have been described as dispersants.On their own,dispersants do not inhibit bacterial growth or kill bacterial pathogens.Both natural,as well as artificial dispersants,are unstable and hydrophobic which necessitate their encapsulation in smart nanocarriers,like p H-responsive micelles,liposomes or hydrogels.Depending on their composition,nanoparticles can also possess intrinsic dispersant properties.Bacteria dispersed from an infectious biofilm end up in the blood circulation where they are cleared by host immune cells.However,this sudden increase in bacterial concentration can also cause sepsis.Simultaneous antibiotic loading of nanoparticles with dispersant properties or combined administration of dispersants and antibiotics can counter this threat.Importantly,biofilm remaining after dispersant administration appears more susceptible to existing antibiotics.Being part of the natural biofilm life-cycle,no signs of"dispersant-resistance"have been observed.Dispersants are therewith promising for the control of infectious biofilms.展开更多
Targeting of chemotherapeutics towards a tumor site by magnetic nanocarriers is considered promising in tumor-control.Magnetic nanoparticles are also considered for use in infection-control as a new means to prevent a...Targeting of chemotherapeutics towards a tumor site by magnetic nanocarriers is considered promising in tumor-control.Magnetic nanoparticles are also considered for use in infection-control as a new means to prevent antimicrobial resistance from becoming the number one cause of death by the year 2050.To this end,magnetic nanoparticles can either be loaded with an antimicrobial for use as a delivery vehicle or modified to acquire intrinsic antimicrobial properties.Magnetic nanoparticles can also be used for the local generation of heat to kill infectious microorganisms.Although appealing for tumor-and infectioncontrol,injection in the blood circulation may yield reticuloendothelial uptake and physical obstruction in organs that yield reduced targeting efficiency.This can be prevented with suitable surface modification.However,precise techniques to direct magnetic nanoparticles towards a target site are lacking.The problem of precise targeting is aggravated in infection-control due to the micrometer-size of infectious biofilms,as opposed to targeting of nanoparticles towards centimeter-sized tumors.This review aims to identify possibilities and impossibilities of magnetic targeting of nanoparticles for infection-control.We first review targeting techniques and the spatial resolution they can achieve as well as surface-chemical modifications of magnetic nanoparticles to enhance their targeting efficiency and antimicrobial efficacy.It is concluded that targeting problems encountered in tumor-control using magnetic nanoparticles,are neglected in most studies on their potential application in infection-control.Currently biofilm targeting by smart,self-adaptive and pH-responsive,antimicrobial nanocarriers for instance,seems easier to achieve than magnetic targeting.This leads to the conclusion that magnetic targeting of nanoparticles for the control of micrometer-sized infectious biofilms may be less promising than initially expected.However,using propulsion rather than precise targeting of magnetic nanoparticles in a magnetic field to traverse through infectious-biofilms can create artificial channels for enhanced antibiotic transport.This is identified as a more feasible,innovative application of magnetic nanoparticles in infection-control than precise targeting and distribution of magnetic nanoparticles over the depth of a biofilm.展开更多
Cascade-reaction chemistry can generate reactive-oxygen-species that can be used for the eradication of infectious biofilms.However,suitable and sufficient oxygen sources are not always available near an infection sit...Cascade-reaction chemistry can generate reactive-oxygen-species that can be used for the eradication of infectious biofilms.However,suitable and sufficient oxygen sources are not always available near an infection site,while the reactive-oxygen-species generated are short-lived.Therefore,we developed a magnetic cascade-reaction container composed of mesoporous Fe_(3)O_(4)@SiO_(2) nanoparticles containing glucose-oxidase and L-arginine for generation of reactive-oxygen-species.Glucose-oxidase was conjugated with APTES facilitating coupling to Fe_(3)O_(4)@SiO_(2) nanoparticles and generation of H_(2)O_(2) from glucose.L-arginine was loaded into the nanoparticles to generate NO from the H_(2)O_(2) generated.Using an externally-applied magnetic field,cascade-reaction containers could be homogeneously distributed across the depth of an infectious biofilm.Cascade-reaction containers with coupled glucose-oxidase were effective in killing planktonic,Gram-positive and Gram-negative bacteria.Additional efficacy of the L-arginine based second cascade-reaction was only observed when H_(2)O_(2) as well as NO were generated in-biofilm.In vivo accumulation of cascade-reaction containers inside abdominal Staphylococcus aureus biofilms upon magnetic targeting was observed real-time in living mice through an implanted,intra-vital window.Moreover,vancomycin-resistant,abdominal S.aureus biofilms could be eradicated consuming solely endogenous glucose,without any glucose addition.Herewith,a new,non-antibiotic-based infection-control strategy has been provided,constituting a welcome addendum to the shrinking clinical armamentarium to control antibiotic-resistant bacterial infections.展开更多
基金financially supported by the National Key Research and Development Program of China(2017YFE0131700)the National Natural Science Foundation of China(52293383)the Soochow University,the Nankai University,and UMCG,Groningen,The Netherlands.
文摘Supported cell membrane coatings meet many requirements set to bioactive nanocarriers and materials,provided sidedness and fluidity of the natural membrane are maintained upon coating.However,the properties of a support-surface responsible for maintaining correct sidedness and fluidity are unknown.Here,we briefly review the properties of natural membranes and membrane-isolation methods,with focus on the asymmetric distribution of functional groups in natural membranes(sidedness)and the ability of molecules to float across a membrane to form functional domains(fluidity).This review concludes that hydrophilic sugar-residues of glycoproteins in the outer-leaflet of cell membranes direct the more hydrophobic inner-leaflet towards a support-surface to create a correctly-sided membrane coating,regardless of electrostatic double-layer interactions.On positively-charged support-surfaces however,strong,electrostatic double-layer attraction of negatively-charged membranes can impede homogeneous coating.In correctly-sided membrane coatings,fluidity is maintained regardless of whether the surface carries a positive or negative charge.However,membranes are frozen on positively-charged,highly-curved,small nanoparticles and localized nanoscopic structures on a support-surface.This leaves an unsupported membrane coating in between nanostructures on planar support-surfaces that is in dual-sided contact with its aqueous environment,yielding enhanced fluidity in membrane coatings on nanostructured,planar support-surfaces as compared with smooth ones.
基金financially supported by the National Natural Science Foundation of China(Nos.21620102005 and 51933006)。
文摘Increasing occurrence of intrinsically antimicrobial-resistant,human pathogens and the protective biofilm-mode in which they grow,dictates a need for the alternative control of infectious biofilms.Biofilm bacteria utilize dispersal mechanisms to detach parts of a biofilm as part of the biofilm life-cycle during times of nutrient scarcity or overpopulation.We here identify recent advances and future challenges in the development of dispersants as a new infection-control strategy.Deoxyribonuclease(DNase)and other extracellular enzymes can disrupt the extracellular matrix of a biofilm to cause dispersal.Also,a variety of small molecules,reactive oxygen species,nitric oxide releasing compounds,peptides and molecules regulating signaling pathways in biofilms have been described as dispersants.On their own,dispersants do not inhibit bacterial growth or kill bacterial pathogens.Both natural,as well as artificial dispersants,are unstable and hydrophobic which necessitate their encapsulation in smart nanocarriers,like p H-responsive micelles,liposomes or hydrogels.Depending on their composition,nanoparticles can also possess intrinsic dispersant properties.Bacteria dispersed from an infectious biofilm end up in the blood circulation where they are cleared by host immune cells.However,this sudden increase in bacterial concentration can also cause sepsis.Simultaneous antibiotic loading of nanoparticles with dispersant properties or combined administration of dispersants and antibiotics can counter this threat.Importantly,biofilm remaining after dispersant administration appears more susceptible to existing antibiotics.Being part of the natural biofilm life-cycle,no signs of"dispersant-resistance"have been observed.Dispersants are therewith promising for the control of infectious biofilms.
基金the National Key Research and Development Program of China(No.2016YFC1100402)the National Natural Science Foundation of China(Nos.11574222 and 21522404)the University Medical Center Groningen(UMCG),The Netherlands。
文摘Targeting of chemotherapeutics towards a tumor site by magnetic nanocarriers is considered promising in tumor-control.Magnetic nanoparticles are also considered for use in infection-control as a new means to prevent antimicrobial resistance from becoming the number one cause of death by the year 2050.To this end,magnetic nanoparticles can either be loaded with an antimicrobial for use as a delivery vehicle or modified to acquire intrinsic antimicrobial properties.Magnetic nanoparticles can also be used for the local generation of heat to kill infectious microorganisms.Although appealing for tumor-and infectioncontrol,injection in the blood circulation may yield reticuloendothelial uptake and physical obstruction in organs that yield reduced targeting efficiency.This can be prevented with suitable surface modification.However,precise techniques to direct magnetic nanoparticles towards a target site are lacking.The problem of precise targeting is aggravated in infection-control due to the micrometer-size of infectious biofilms,as opposed to targeting of nanoparticles towards centimeter-sized tumors.This review aims to identify possibilities and impossibilities of magnetic targeting of nanoparticles for infection-control.We first review targeting techniques and the spatial resolution they can achieve as well as surface-chemical modifications of magnetic nanoparticles to enhance their targeting efficiency and antimicrobial efficacy.It is concluded that targeting problems encountered in tumor-control using magnetic nanoparticles,are neglected in most studies on their potential application in infection-control.Currently biofilm targeting by smart,self-adaptive and pH-responsive,antimicrobial nanocarriers for instance,seems easier to achieve than magnetic targeting.This leads to the conclusion that magnetic targeting of nanoparticles for the control of micrometer-sized infectious biofilms may be less promising than initially expected.However,using propulsion rather than precise targeting of magnetic nanoparticles in a magnetic field to traverse through infectious-biofilms can create artificial channels for enhanced antibiotic transport.This is identified as a more feasible,innovative application of magnetic nanoparticles in infection-control than precise targeting and distribution of magnetic nanoparticles over the depth of a biofilm.
基金financially supported by the National Natural Science Foundation of China(51933006,21620102005)The Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2018PT35031).
文摘Cascade-reaction chemistry can generate reactive-oxygen-species that can be used for the eradication of infectious biofilms.However,suitable and sufficient oxygen sources are not always available near an infection site,while the reactive-oxygen-species generated are short-lived.Therefore,we developed a magnetic cascade-reaction container composed of mesoporous Fe_(3)O_(4)@SiO_(2) nanoparticles containing glucose-oxidase and L-arginine for generation of reactive-oxygen-species.Glucose-oxidase was conjugated with APTES facilitating coupling to Fe_(3)O_(4)@SiO_(2) nanoparticles and generation of H_(2)O_(2) from glucose.L-arginine was loaded into the nanoparticles to generate NO from the H_(2)O_(2) generated.Using an externally-applied magnetic field,cascade-reaction containers could be homogeneously distributed across the depth of an infectious biofilm.Cascade-reaction containers with coupled glucose-oxidase were effective in killing planktonic,Gram-positive and Gram-negative bacteria.Additional efficacy of the L-arginine based second cascade-reaction was only observed when H_(2)O_(2) as well as NO were generated in-biofilm.In vivo accumulation of cascade-reaction containers inside abdominal Staphylococcus aureus biofilms upon magnetic targeting was observed real-time in living mice through an implanted,intra-vital window.Moreover,vancomycin-resistant,abdominal S.aureus biofilms could be eradicated consuming solely endogenous glucose,without any glucose addition.Herewith,a new,non-antibiotic-based infection-control strategy has been provided,constituting a welcome addendum to the shrinking clinical armamentarium to control antibiotic-resistant bacterial infections.
