Since the emergence of cancer nanomedicine, researchers have had intense interest in developing nanoparticles （NPs） that can specifically target diseased sites while avoiding healthy tissue to mitigate the off-targe...Since the emergence of cancer nanomedicine, researchers have had intense interest in developing nanoparticles （NPs） that can specifically target diseased sites while avoiding healthy tissue to mitigate the off-target effects seen with conventional treatments like chemotherapy. Initial endeavors focused on the bioconjugation of targeting agents to NPs, and more recently, researchers have begun to develop biomimetic NP platforms that can avoid immune recognition to maximally accumulate in tumors. In this review, we describe the advantages and limitations of each of these targeting strategies. First, we review developments in bioconjugation strategies, where NPs are coated with biomolecules such as antibodies, aptamers, peptides, and small molecules to enable cell-specific binding. While bioconjugated NPs offer many exciting features and have improved pharmacokinetics and biodistribution relative to unmodified NPs, they are still recognized by the body as ＂foreign＂, resulting in their clearance by the mononuclear phagocytic system （MPS）. To overcome this limitation, researchers have recently begun to investigate biomimetic approaches that can hide NPs from immune recognition and reduce clearance by the MPS. These biomimetic NPs fall into two distinct categories： synthetic NPs that present naturally occurring structures, and NPs that are completely disguised by natural structures. Overall bioconjugated and biomimetic NPs have substantial potential to improve upon conventional treatments by reducing off-target effects through site-specific delivery. and they show great promise for future standards of care. Here, we provide a summary of each strategy, discuss considerations for their design moving forward, and highlight their potential clinical impact on cancer therapy.展开更多
Supramolecular proteins are generated using a limited set of twenty amino acids,but have distinctive functionalities which arise from the sequential arrangement of amino acids configured to exquisite three-dimensional...Supramolecular proteins are generated using a limited set of twenty amino acids,but have distinctive functionalities which arise from the sequential arrangement of amino acids configured to exquisite three-dimensional structures.Viruses,virus-like particles,ferritins,enzyme complexes,cellular micro-compartments,and other supramolecular protein assemblies exemplify these systems,with their precise arrangements of tens to hundreds of molecules into highly organized scaffolds for nucleic acid packaging,metal storage,catalysis or sequestering reactions at the nanometer scale.These versatile protein systems,dubbed as bionanoparticles(BNPs),have attracted materials scientists to seek new opportunities with these pre-fabricated templates in a wide range of nanotechnology-related applications.Here,we focus on some of the key modification strategies that have been utilized,ranging from basic protein conjugation techniques to more novel strategies,to expand the functionalities of these multimeric protein assemblies.Ultimately,in combination with molecular cloning and sophisticated chemistries,these BNPs are being incorporated into many applications ranging from functional materials to novel biomedical drug designs.展开更多
Using biological templates to build one-dimensional functional materials holds great promise in developing nanosized electrical devices,sensors,catalysts,and energy storage units.In this communication,we report a vers...Using biological templates to build one-dimensional functional materials holds great promise in developing nanosized electrical devices,sensors,catalysts,and energy storage units.In this communication,we report a versatile assembly process for the preparation of water-soluble conductive polyaniline(PANi)/M13 composite nanowires by employing the bacteriophage M13 as a template.The surface lysine residues of M13 can be derivatized with carboxylic groups to improve its binding ability to the aniline;the resulting modifi ed M13 is denoted as m-M13.Highly negatively-charged poly(sulfonated styrene)was used both as a dopant acid and a stabilizing agent to enhance the stability of the composite fi bers in aqueous solution.A transparent solution of the conductive PANi/m-M13 composite fi bers can be readily obtained without any further purifi cation step.The fi bers can be easily fabricated into thin conductive fi lms due to their high aspect ratio and good solubility in aqueous solution.This synthesis discloses a unique and versatile way of using bionanorods to produce composite fi brillar materials with narrow dispersity,high aspect ratio,and high processibility,which may have many potential applications in electronics,optics,sensing,and biomedical engineering.展开更多
Biological application of conjugates derived from oligonucleotides and quinone methides have pre- viously been limited by the slow exchange of their covalent self-adducts and subsequent alkylation of target nucleic ac...Biological application of conjugates derived from oligonucleotides and quinone methides have pre- viously been limited by the slow exchange of their covalent self-adducts and subsequent alkylation of target nucleic acids. To enhance the rates of these processes, a new quinone methide precursor with an electron donating substituent has been prepared. Additionally, this substi- tuent has been placed para to the nascent exo-methylene group of the quinone methide for maximum effect. A conjugate made from this precursor and a 5＇-aminohex- yloligonucleotide accelerates formation of its reversible self-adduct and alkylation of its complementary DNA as predicted from prior model studies.展开更多
A generic method was described to change surface biocompatibihty by introducing reactive functional groups onto surfaces of polymeric substrates and covalently binding them with biomolecules.A block copolymer with pro...A generic method was described to change surface biocompatibihty by introducing reactive functional groups onto surfaces of polymeric substrates and covalently binding them with biomolecules.A block copolymer with protected carboxylic acid functionality,poly（styrene-b-tert-butyl acrylate）（PS-PtBA）,was spin coated from solutions in toluene on a bioinert polystyrene（PS） substrate to form a bilayer structure：a surface layer of the poly（tert-butyl acrylate）（PtBA） blocks that order at the air-polymer interface and a bottom layer of the PS blocks that entangle with the PS substrate.The thickness of the PtBA layer and the area density of tert-butyl ester groups of PtBA increased linearly with the concentration of the spin coating solution until a 2 nm saturated monolayer coverage of PtBA was achieved at the concentration of 0.4%W/W.The protected carboxylic acid groups were generated by exposing the tert-butyl ester groups of PtBA to trifluoroacetic acid （TFA） for bioconjugation with FMRF peptides via amide bonds.The yield of the bioconjugation reaction for the saturated surface was calculated to be 37.1%based on X-ray photoelectron spectroscopy（XPS） measurements.The success of each functionalization step was demonstrated and characterized by XPS and contact angle measurements.This polymer functionalization/modification concept can be virtually applied to any polymeric substrate by choosing appropriate functional block copolymers and biomolecules to attain novel biocompatibility.展开更多
Comprehensive Summary Interfacing DNA oligonucleotides and DNA aptamers with gold nanoparticles has generated numerous functional hybrid materials for sensing,self-assembly and drug delivery applications.Our lab has b...Comprehensive Summary Interfacing DNA oligonucleotides and DNA aptamers with gold nanoparticles has generated numerous functional hybrid materials for sensing,self-assembly and drug delivery applications.Our lab has been working in this area for 15 years.In this article,the current understanding of the adsorption of DNA to gold nanoparticles is summarized,and related applications in bioconjugation of DNA to gold surface is described.In addition,problems of using gold nanoparticles to signaling aptamer binding are discussed.Finally,re-selection of aptamers for previously reported targets using the library-immobilization method is reviewed.展开更多
For a significant duration,enhancing the efficacy of cancer therapy has remained a critical concern.Magnetotactic bacteria(MTB),often likened to micro-robots,hold substantial promise as a drug delivery system.MTB,clas...For a significant duration,enhancing the efficacy of cancer therapy has remained a critical concern.Magnetotactic bacteria(MTB),often likened to micro-robots,hold substantial promise as a drug delivery system.MTB,classified as anaerobic,aquatic,and gram-negative microorganisms,exhibit remarkable motility and precise control over their internal biomineralization processes.This unique ability results in the formation of magnetic nanoparticles arranged along filamentous structures in a catenary fashion,enclosed within a membrane.These bacteria possess distinctive biochemical properties that facilitate their precise positioning within complex environments.By harnessing these biochemical attributes,MTB could potentially offer substantial advantages in the realm of cancer therapy.This article reviews the drug delivery capabilities of MTB in tumor treatment and explores various applications based on their inherent properties.The objective is to provide a comprehensive understanding of MTB-driven drug delivery and stimulate innovative insights in this field.展开更多
Degradable polyesters have long been regarded as eco-friendly materials,useful for various applicationswhile meeting the growing needs of sustainability.However,it is still challenging to synthesize functional aliphat...Degradable polyesters have long been regarded as eco-friendly materials,useful for various applicationswhile meeting the growing needs of sustainability.However,it is still challenging to synthesize functional aliphatic polyesters from abundant and cheap renewable sources.Our present study reports a readily available and versatile platform for producing functional and stereoregular aliphatic polyesters from 4-hydroxy-L-proline(4-HYP).We synthesized a bicyclic bridged lactone monomer,namely,NR-PL,by a simple and scalable two-step process allowing facile side-chain functionalization and derivatization.The ring-opening homopolymerization and copolymerization for the generation of N^(R)-PL were controlled fully by using organobases such as 1,8-diazabicyclo[5.4.0]-undec-7-ene(DBU)without any detectable epimerization.This process afforded stereoregular polyesters PNRPE with molar mass(M_(n))up to 90 kg/mol and a narrow dispersity(Ð)generally below 1.10.The uniqueness of the backbone,which contains two chiral centers on a rigid propyl ring,together with the versatility of the side chain,offer tunable properties complementary to existing aliphatic polyesters.The utility of the polymers was showcased by the facile site-specific bioconjugation of PN^(EG3)PE,a water-soluble polyester,to a protein.This work might open numerous opportunities in creating functional and sustainable polyesters for a wide range of applications,including degradable plastics,drug delivery,and protein therapeutics.展开更多
Monodispersed microspheres with polystyrene as the core and poly（acrylamide-co-N-acryloxysuccinirnide） as the shell were synthesized by a two-step surfactant-free emulsion copolymerization.The core-shell morphology ...Monodispersed microspheres with polystyrene as the core and poly（acrylamide-co-N-acryloxysuccinirnide） as the shell were synthesized by a two-step surfactant-free emulsion copolymerization.The core-shell morphology of the microspheres was shown by scanning electron microscopy and transmission electron microscopy.Rabbit immunoglobulin G （as antigen） was covalently coupled onto the microspheres by the reaction between succinimide-activated ester groups on the shell of the microspheres and amino groups of the antigen molecules.The size of particles was characterized by dynamic light scattering technique and was found to vary upon bioconjugation and interaction with proteins.The binding process was shown to be specific to goat anti-rabbit immunoglobulin G（as antibody） and reversible upon the addition of free antigen into the system.展开更多
A new pyridoxal-5-phosphate （PLP） derivative FHMDP was developed for the transamination of different pep- tides with three most hindered amino acid residues （Leu, Ile, Val） as their N-terminus. Compared to the pre...A new pyridoxal-5-phosphate （PLP） derivative FHMDP was developed for the transamination of different pep- tides with three most hindered amino acid residues （Leu, Ile, Val） as their N-terminus. Compared to the previously reported reactions of PLP derivatives, the N-terminus transamination could be accomplished efficiently with the new compound.展开更多
Objective:This study aimed to describe,optimize and evaluate a method for preparing multivalent conjugate vaccines by simultaneous conjugation of two different bacterial capsular polysaccharides(CPs)with tetanus toxoi...Objective:This study aimed to describe,optimize and evaluate a method for preparing multivalent conjugate vaccines by simultaneous conjugation of two different bacterial capsular polysaccharides(CPs)with tetanus toxoid(TT)as bivalent conjugates.Methods:Different molecular weights(MWs)of polysaccharides,activating agents and capsular polysaccharide/protein(CP/Pro)ratio that may influence conjugation and immunogenicity were investigated and optimized to prepare the bivalent conjugate bulk.Using the described method and optimized parameters,a 20-valent pneumococcal conjugate vaccine and a bivalent meningococcal vaccine were developed and their effectiveness was compared to that of corresponding licensed vaccines in rabbit or mouse models.Results:The immunogenicity test revealed that polysaccharides with lower MWs were better for Pn1-TT-Pn3 and MenA-TT-MenC,while higher MWs were superior for Pn4-TT-Pn14,Pn6A-TT-Pn6B,Pn7F-TT-Pn23F and Pn8-TT-Pn11A.For activating polysaccharides,1-cyano-4-dimethylaminopyridinium tetrafluoroborate(CDAP)was superior to cyanogen bromide(CNBr),but for Pn1,Pn3 and MenC,N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride(EDAC)was the most suitable option.For Pn6A-TT-Pn6B and Pn8-TT-Pn11A,rabbits immunized with bivalent conjugates with lower CP/Pro ratios showed significantly stronger CP-specific antibody responses,while for Pn4-TT-Pn14,higher CP/Pro ratio was better.Instead of interfering with the respective immunological activity,our bivalent conjugates usually induced higher IgG titers than their monovalent counterparts.Conclusion:The result indicated that the described conjugation technique was feasible and efficacious to prepare glycoconjugate vaccines,laying a solid foundation for developing extended-valent multivalent or combined conjugate vaccines without potentially decreased immune function.展开更多
文摘Since the emergence of cancer nanomedicine, researchers have had intense interest in developing nanoparticles （NPs） that can specifically target diseased sites while avoiding healthy tissue to mitigate the off-target effects seen with conventional treatments like chemotherapy. Initial endeavors focused on the bioconjugation of targeting agents to NPs, and more recently, researchers have begun to develop biomimetic NP platforms that can avoid immune recognition to maximally accumulate in tumors. In this review, we describe the advantages and limitations of each of these targeting strategies. First, we review developments in bioconjugation strategies, where NPs are coated with biomolecules such as antibodies, aptamers, peptides, and small molecules to enable cell-specific binding. While bioconjugated NPs offer many exciting features and have improved pharmacokinetics and biodistribution relative to unmodified NPs, they are still recognized by the body as ＂foreign＂, resulting in their clearance by the mononuclear phagocytic system （MPS）. To overcome this limitation, researchers have recently begun to investigate biomimetic approaches that can hide NPs from immune recognition and reduce clearance by the MPS. These biomimetic NPs fall into two distinct categories： synthetic NPs that present naturally occurring structures, and NPs that are completely disguised by natural structures. Overall bioconjugated and biomimetic NPs have substantial potential to improve upon conventional treatments by reducing off-target effects through site-specific delivery. and they show great promise for future standards of care. Here, we provide a summary of each strategy, discuss considerations for their design moving forward, and highlight their potential clinical impact on cancer therapy.
文摘Supramolecular proteins are generated using a limited set of twenty amino acids,but have distinctive functionalities which arise from the sequential arrangement of amino acids configured to exquisite three-dimensional structures.Viruses,virus-like particles,ferritins,enzyme complexes,cellular micro-compartments,and other supramolecular protein assemblies exemplify these systems,with their precise arrangements of tens to hundreds of molecules into highly organized scaffolds for nucleic acid packaging,metal storage,catalysis or sequestering reactions at the nanometer scale.These versatile protein systems,dubbed as bionanoparticles(BNPs),have attracted materials scientists to seek new opportunities with these pre-fabricated templates in a wide range of nanotechnology-related applications.Here,we focus on some of the key modification strategies that have been utilized,ranging from basic protein conjugation techniques to more novel strategies,to expand the functionalities of these multimeric protein assemblies.Ultimately,in combination with molecular cloning and sophisticated chemistries,these BNPs are being incorporated into many applications ranging from functional materials to novel biomedical drug designs.
基金We are grateful for financial support from NSF-DMR-0706431,NSF career award,US DoD,and the W.M.Keck Foundation.This manuscript has been approved by the U.S.Army Natick Soldier Research,Development and Engineering Center for unlimited distribution(PAO#08-107).
文摘Using biological templates to build one-dimensional functional materials holds great promise in developing nanosized electrical devices,sensors,catalysts,and energy storage units.In this communication,we report a versatile assembly process for the preparation of water-soluble conductive polyaniline(PANi)/M13 composite nanowires by employing the bacteriophage M13 as a template.The surface lysine residues of M13 can be derivatized with carboxylic groups to improve its binding ability to the aniline;the resulting modifi ed M13 is denoted as m-M13.Highly negatively-charged poly(sulfonated styrene)was used both as a dopant acid and a stabilizing agent to enhance the stability of the composite fi bers in aqueous solution.A transparent solution of the conductive PANi/m-M13 composite fi bers can be readily obtained without any further purifi cation step.The fi bers can be easily fabricated into thin conductive fi lms due to their high aspect ratio and good solubility in aqueous solution.This synthesis discloses a unique and versatile way of using bionanorods to produce composite fi brillar materials with narrow dispersity,high aspect ratio,and high processibility,which may have many potential applications in electronics,optics,sensing,and biomedical engineering.
文摘Biological application of conjugates derived from oligonucleotides and quinone methides have pre- viously been limited by the slow exchange of their covalent self-adducts and subsequent alkylation of target nucleic acids. To enhance the rates of these processes, a new quinone methide precursor with an electron donating substituent has been prepared. Additionally, this substi- tuent has been placed para to the nascent exo-methylene group of the quinone methide for maximum effect. A conjugate made from this precursor and a 5＇-aminohex- yloligonucleotide accelerates formation of its reversible self-adduct and alkylation of its complementary DNA as predicted from prior model studies.
文摘A generic method was described to change surface biocompatibihty by introducing reactive functional groups onto surfaces of polymeric substrates and covalently binding them with biomolecules.A block copolymer with protected carboxylic acid functionality,poly（styrene-b-tert-butyl acrylate）（PS-PtBA）,was spin coated from solutions in toluene on a bioinert polystyrene（PS） substrate to form a bilayer structure：a surface layer of the poly（tert-butyl acrylate）（PtBA） blocks that order at the air-polymer interface and a bottom layer of the PS blocks that entangle with the PS substrate.The thickness of the PtBA layer and the area density of tert-butyl ester groups of PtBA increased linearly with the concentration of the spin coating solution until a 2 nm saturated monolayer coverage of PtBA was achieved at the concentration of 0.4%W/W.The protected carboxylic acid groups were generated by exposing the tert-butyl ester groups of PtBA to trifluoroacetic acid （TFA） for bioconjugation with FMRF peptides via amide bonds.The yield of the bioconjugation reaction for the saturated surface was calculated to be 37.1%based on X-ray photoelectron spectroscopy（XPS） measurements.The success of each functionalization step was demonstrated and characterized by XPS and contact angle measurements.This polymer functionalization/modification concept can be virtually applied to any polymeric substrate by choosing appropriate functional block copolymers and biomolecules to attain novel biocompatibility.
文摘Comprehensive Summary Interfacing DNA oligonucleotides and DNA aptamers with gold nanoparticles has generated numerous functional hybrid materials for sensing,self-assembly and drug delivery applications.Our lab has been working in this area for 15 years.In this article,the current understanding of the adsorption of DNA to gold nanoparticles is summarized,and related applications in bioconjugation of DNA to gold surface is described.In addition,problems of using gold nanoparticles to signaling aptamer binding are discussed.Finally,re-selection of aptamers for previously reported targets using the library-immobilization method is reviewed.
基金supported by the National Natural Science Foundation of China(No.3190110313 to K.Ma)Special Foundation of President of the Chinese Academy of Sciences(No.YZJJ2022QN_(4)4)+2 种基金HFIPS Director’s Fund(Nos.E16CWK123X1YZJJQY202201)the Heye Health Technology Chong Ming Project(No.HYCMP-2022012 to Y.Wang)。
文摘For a significant duration,enhancing the efficacy of cancer therapy has remained a critical concern.Magnetotactic bacteria(MTB),often likened to micro-robots,hold substantial promise as a drug delivery system.MTB,classified as anaerobic,aquatic,and gram-negative microorganisms,exhibit remarkable motility and precise control over their internal biomineralization processes.This unique ability results in the formation of magnetic nanoparticles arranged along filamentous structures in a catenary fashion,enclosed within a membrane.These bacteria possess distinctive biochemical properties that facilitate their precise positioning within complex environments.By harnessing these biochemical attributes,MTB could potentially offer substantial advantages in the realm of cancer therapy.This article reviews the drug delivery capabilities of MTB in tumor treatment and explores various applications based on their inherent properties.The objective is to provide a comprehensive understanding of MTB-driven drug delivery and stimulate innovative insights in this field.
基金National Natural Science Foundation of China(21722401 for H.Lu and 21634001 for E.Q.Chen).
文摘Degradable polyesters have long been regarded as eco-friendly materials,useful for various applicationswhile meeting the growing needs of sustainability.However,it is still challenging to synthesize functional aliphatic polyesters from abundant and cheap renewable sources.Our present study reports a readily available and versatile platform for producing functional and stereoregular aliphatic polyesters from 4-hydroxy-L-proline(4-HYP).We synthesized a bicyclic bridged lactone monomer,namely,NR-PL,by a simple and scalable two-step process allowing facile side-chain functionalization and derivatization.The ring-opening homopolymerization and copolymerization for the generation of N^(R)-PL were controlled fully by using organobases such as 1,8-diazabicyclo[5.4.0]-undec-7-ene(DBU)without any detectable epimerization.This process afforded stereoregular polyesters PNRPE with molar mass(M_(n))up to 90 kg/mol and a narrow dispersity(Ð)generally below 1.10.The uniqueness of the backbone,which contains two chiral centers on a rigid propyl ring,together with the versatility of the side chain,offer tunable properties complementary to existing aliphatic polyesters.The utility of the polymers was showcased by the facile site-specific bioconjugation of PN^(EG3)PE,a water-soluble polyester,to a protein.This work might open numerous opportunities in creating functional and sustainable polyesters for a wide range of applications,including degradable plastics,drug delivery,and protein therapeutics.
基金supported by the National Natural Science Foundation of China(Nos.20328407,50673045) and the Canada Research Chair program
文摘Monodispersed microspheres with polystyrene as the core and poly（acrylamide-co-N-acryloxysuccinirnide） as the shell were synthesized by a two-step surfactant-free emulsion copolymerization.The core-shell morphology of the microspheres was shown by scanning electron microscopy and transmission electron microscopy.Rabbit immunoglobulin G （as antigen） was covalently coupled onto the microspheres by the reaction between succinimide-activated ester groups on the shell of the microspheres and amino groups of the antigen molecules.The size of particles was characterized by dynamic light scattering technique and was found to vary upon bioconjugation and interaction with proteins.The binding process was shown to be specific to goat anti-rabbit immunoglobulin G（as antibody） and reversible upon the addition of free antigen into the system.
基金Project supported by the National Natural Science Foundation of China （Nos. 20932006 and 21002056）.
文摘A new pyridoxal-5-phosphate （PLP） derivative FHMDP was developed for the transamination of different pep- tides with three most hindered amino acid residues （Leu, Ile, Val） as their N-terminus. Compared to the previously reported reactions of PLP derivatives, the N-terminus transamination could be accomplished efficiently with the new compound.
文摘Objective:This study aimed to describe,optimize and evaluate a method for preparing multivalent conjugate vaccines by simultaneous conjugation of two different bacterial capsular polysaccharides(CPs)with tetanus toxoid(TT)as bivalent conjugates.Methods:Different molecular weights(MWs)of polysaccharides,activating agents and capsular polysaccharide/protein(CP/Pro)ratio that may influence conjugation and immunogenicity were investigated and optimized to prepare the bivalent conjugate bulk.Using the described method and optimized parameters,a 20-valent pneumococcal conjugate vaccine and a bivalent meningococcal vaccine were developed and their effectiveness was compared to that of corresponding licensed vaccines in rabbit or mouse models.Results:The immunogenicity test revealed that polysaccharides with lower MWs were better for Pn1-TT-Pn3 and MenA-TT-MenC,while higher MWs were superior for Pn4-TT-Pn14,Pn6A-TT-Pn6B,Pn7F-TT-Pn23F and Pn8-TT-Pn11A.For activating polysaccharides,1-cyano-4-dimethylaminopyridinium tetrafluoroborate(CDAP)was superior to cyanogen bromide(CNBr),but for Pn1,Pn3 and MenC,N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride(EDAC)was the most suitable option.For Pn6A-TT-Pn6B and Pn8-TT-Pn11A,rabbits immunized with bivalent conjugates with lower CP/Pro ratios showed significantly stronger CP-specific antibody responses,while for Pn4-TT-Pn14,higher CP/Pro ratio was better.Instead of interfering with the respective immunological activity,our bivalent conjugates usually induced higher IgG titers than their monovalent counterparts.Conclusion:The result indicated that the described conjugation technique was feasible and efficacious to prepare glycoconjugate vaccines,laying a solid foundation for developing extended-valent multivalent or combined conjugate vaccines without potentially decreased immune function.
