Emerging infectious diseases are major threats to human health.Most severe viral disease outbreaks occur in developing regions where health conditions are poor.With increased international travel and business,the poss...Emerging infectious diseases are major threats to human health.Most severe viral disease outbreaks occur in developing regions where health conditions are poor.With increased international travel and business,the possibility of eventually transmitting infectious viruses between different countries is increasing.The most effective approach in preventing viral diseases is vaccination.However,vaccines are not currently available for numerous viral diseases.Viruslike particles(VLPs) are engineered vaccine candidates that have been studied for decades.VLPs are constructed by viral protein expression in various expression systems that promote the selfassembly of proteins into structures resembling virus particles.VLPs have antigenicity similar to that of the native virus,but are non-infectious as they lack key viral genetic material.VLP vaccines have attracted considerable research interest because they offer several advantages over traditional vaccines.Studies have shown that VLP vaccines can stimulate both humoral and cellular immune responses,which may offer effective antiviral protection.Here we review recent developments with VLP-based vaccines for several highly virulent emerging or re-emerging infectious diseases.The infectious agents discussed include RNA viruses from different virus families,such as the Arenaviridae,Bunyaviridae,Caliciviridae,Coronaviridae,Filoviridae,Flaviviridae,Orthomyxoviridae,Paramyxoviridae,and Togaviridae families.展开更多
Ebola virus （EBOV） is a key member of Filoviridae family and causes severe human infectious diseases with high morbidity and mortality. As a typical negative-sense single-stranded RNA （-ssRNA） viruses, EBOV posses...Ebola virus （EBOV） is a key member of Filoviridae family and causes severe human infectious diseases with high morbidity and mortality. As a typical negative-sense single-stranded RNA （-ssRNA） viruses, EBOV possess a nucleocapsid protein （NP） to facilitate genomic RNA encapsidation to form viral ribonucleoprotein complex （RNP） together with genome RNA and polymerase, which plays the most essential role in virus proliferation cycle. However, the mechanism of EBOV RNP formation remains unclear. In this work, we solved the high resolution structure of core domain of EBOV NP. The polypeptide of EBOV NP core domain （NPcore） pos- sesses an N-lobe and C-lobe to clamp a RNA binding groove, presenting similarities with the structures of the other reported viral NPs encoded by the members from Mononegavirales order. Most strikingly, a hydrophobic pocket at the surface of the C-lobe is occupied by an a- helix of EBOV NPcore itself, which is highly conserved among filoviridae family. Combined with other bio- chemical and biophysical evidences, our results provides great potential for understanding the mechanism underlying EBOV RNP formation via the mobility of EBOV NP element and enables the development of antiviral therapies targeting EBOV RNP formation.展开更多
Varicella-zoster is a highly communicable virus that can be transmitted through the airborne route.About one quarter of people are infected with this virus.Previous studies have described the structure of A-capsid and...Varicella-zoster is a highly communicable virus that can be transmitted through the airborne route.About one quarter of people are infected with this virus.Previous studies have described the structure of A-capsid and a blurred reconstruction of the C-capsid with icosahedral symmetry.In this study,we have determined the more precise detailed structures of the varicella-zoster virus(VZV)B-and C-capsid in icosahedral symmetry using a combination of block-based reconstruction and symmetry relaxation strategies.In addition,we are reporting structural details of the portal vertex reconstructions in five-fold symmetry and portal reconstructions in twelve-fold symmetry.The structures unveil the basis for the high thermal stability of the VZV capsid.The conformational flexibility of structural elements of the capsid plays a role in the assembly of the capsid and drives processes critical for the viral life cycle.The results of the study open up new avenues for the development of drugs against a highly prevalent and contagious pathogen.展开更多
The Phytoreovirus rice dwarf virus (RDV) has a complex nucleocapsid architecture composed of multiple proteins and RNAs. However, specific RNA-protein and protein-protein interactions involved in virion packaging have...The Phytoreovirus rice dwarf virus (RDV) has a complex nucleocapsid architecture composed of multiple proteins and RNAs. However, specific RNA-protein and protein-protein interactions involved in virion packaging have not been entirely elucidated. In order to define mechanisms governing RDV particle assembly, interactions between individual components were analyzed both in vivo and in vitro. The P7 core protein binds specifically and with high affinity to all 12 genomic RDV dsRNAs. P1, a putative RNA polymerase, P5, a putative guanyltransferase and P7 are encapsidated within the virion and also bind viral transcripts based upon in vitro binding assays. P1, P5, P7 and genomic dsRNAs were lacking in empty particles purified from infected tissues that also yielded fractions containing intact, infectious particles. In addition, P7 forms complexes with P1 and P3, a core capsid protein, in viral particles. These results indicate the possibility that core proteins and dsRNAs interact as one unit suggesting a mechanism for assortment of viral RNAs and subsequent packaging into core particles.展开更多
The first appearance of lipid rafts, or lipid rafts-like structure, was occasionally observed by cryo-electronic microscopy in 1980s as cavity, such as caveolae. However, the fully understanding of lipid raft was attr...The first appearance of lipid rafts, or lipid rafts-like structure, was occasionally observed by cryo-electronic microscopy in 1980s as cavity, such as caveolae. However, the fully understanding of lipid raft was attributed by the studies of T cell activation, virus entry/budding, and other membrane events. During the interaction of T cell and antigen presenting cell, a highly organized structure is formed at the interface of the two cells, where cholesterol and sphingolipids are enriched, and form a liquid ordered phase that facilitates the signaling proteins on and off. Lipid rafts are also involved in virus entry and assembly. In this review, we will discuss cholesterolsphingolipid floating microdomain, the lipid raft as a unique compartment of the plasma membrane, with biological functions that ensure correct intracellular traffic of proteins and lipids, such as protein-protein interactions by concentrating certain proteins in these microdomains, while excluding others. We also discuss the disruption of lipid rafts is related to different diseases and aging, and we especially exploit the lipid rafts as pharmaceutical targets for anti-virus and anti-inflammation, particularly a new approach to control HIV infection for AIDS prevention and protection by inhibition or disruption of lipid rafts. Cellular ＆ Molecular Immunology.展开更多
Torque teno virus(TTV) is a nonenveloped virus containing a single-stranded,circular DNA genome of approximately 3.8kb.We completely synthesized the 3 808 nucleotides of the TTV(SANBAN isolate) genome,which contains a...Torque teno virus(TTV) is a nonenveloped virus containing a single-stranded,circular DNA genome of approximately 3.8kb.We completely synthesized the 3 808 nucleotides of the TTV(SANBAN isolate) genome,which contains a hairpin structure and a GC-rich region.More than 100 overlapping oligonucleotides were chemically synthesized and assembled by polymerase chain assembly reaction(PCA),and the synthesis was completed with splicing by overlap extension(SOEing).This study establishes the methodological basis of the chemical synthesis of a viral genome for use as a live attenuated vaccine or gene therapy vector.展开更多
目的通过改变原噬菌体ms2包膜蛋白RNA包装位点（19碱基的茎环结构）的数量及亲和力，构建新的原核表达系统，探讨表达内含长片段（达到理论上的1900bp）RNA的耐RNase病毒样颗粒的可能性。方法首先设计含HindⅢ和NotⅠ酶切位点的引物，扩...目的通过改变原噬菌体ms2包膜蛋白RNA包装位点（19碱基的茎环结构）的数量及亲和力，构建新的原核表达系统，探讨表达内含长片段（达到理论上的1900bp）RNA的耐RNase病毒样颗粒的可能性。方法首先设计含HindⅢ和NotⅠ酶切位点的引物，扩增ms2包膜蛋白的编码成熟酶蛋白和衣壳蛋白的1700bp序列，并将原来的19mer的包装位点序列改变为C-5变异体（19 bp stem-loop结构中-5位的尿嘧啶改变为胞嘧啶），HindⅢ和NotⅠ酶切后，与用同样酶切的表达载体pET-28（b）相连接，得到重组载体pET-ms2-pac。应用重叠PCR扩增3种病毒的5段嵌合体序列（包括3段SARS-CoV基因、一段HCV基因和一段H5N1基因），并在SARS-CoV3和HCV序列之间插入一个19mer的变异体包装位点序列，在设计引物时，使嵌合体两端含有NotⅠ酶切位点，与NotⅠ酶切的重组载体pET-ms2-pac相连接，构建得到具有2个变异包装位点的表达载体pET-ms2-3V。同时构建3种对照重组表达载体，分别测定N-P3V-pET-P、N-P3V-pET-C、P-3V-pET-P和pET-ms2-3 V 4种重组表达质粒表达产物的260nm吸光度（A260）值，根据公式A260=0．125mg／ml计算4种表达产物的表达效率。结果成功构建了4种原核表达载体：pET-ms2-3V、P-3V-pET-P、N-P3V-pET-P和N-P3V-pET-C。pET-ms2-3V和P-3V-pET-P经原核表达后得到含全长为1891的5段嵌合体RNA的病毒样颗粒；N-P3V-pET-P、N-P3V-pET-C其原核表达产物病毒样颗粒中仅包装了1200bp的目的嵌合体RNA。N-P3V-pET-P、N-P3V-pET-C、P-3V-pET-P和pET-ms2-3V的表达效率分别为0．23、0．35、0．35和0．51mg／ml。N-P3V-pET-C比N-P3V-pET-P表达效率高52％，而pET-ms2-3V比P-3V-pET-P表达效率高38％。所包装的RNA具有耐RNase和DNase消化的特性以及良好的不同温度条件下的稳定性。结论通过改变噬菌体ms2 RNA包装位点（19碱基的茎环结构）的数量，可构建能表达内含达到理论上的约1900bp外源RNA�展开更多
Viruses in the family Reoviridae are non-enveloped particles comprising a segmented double-stranded RNA genome surrounded by a two-layered or multi-layered icosahedral protein capsid.These viruses are classified into ...Viruses in the family Reoviridae are non-enveloped particles comprising a segmented double-stranded RNA genome surrounded by a two-layered or multi-layered icosahedral protein capsid.These viruses are classified into two sub-families based on their particle structural organization.Recent studies have focused on high-resolution three-dimensional structures of reovirus particles by using cryo-electron microscopy (cryo-EM) to approach the resolutions seen in X-ray crystallographic structures.The results of cryo-EM image reconstructions allow tracing of most of the protein side chains,and thus permit integration of structural and functional information into a coherent mechanism for reovirus assembly and entry.展开更多
Transformation-associated recombination(TAR)has been widely used to assemble large DNA constructs.One of the significant obstacles hindering assembly efficiency is the presence of error-prone DNA repair pathways in ye...Transformation-associated recombination(TAR)has been widely used to assemble large DNA constructs.One of the significant obstacles hindering assembly efficiency is the presence of error-prone DNA repair pathways in yeast,which results in vector backbone recircularization or illegitimate recombination products.To increase TAR assembly efficiency,we prepared a dual-selective TAR vector,pGFCS,by adding a PADH1-URA3 cassette to a previously described yeast-bacteria shuttle vector,p GF,harboring a PHIS3–HIS3 cassette as a positive selection marker.This new cassette works as a negative selection marker to ensure that yeast harboring a recircularized vector cannot propagate in the presence of 5-fluoroorotic acid.To prevent pGFCS bearing ura3 from recombining with endogenous ura3-52 in the yeast genome,a highly transformable Saccharomyces cerevisiae strain,VL6-48B,was prepared by chromosomal substitution of ura3-52 with a transgene conferring resistance to blasticidin.A55-kb genomic fragment of monkeypox virus encompassing primary detection targets for quantitative PCR was assembled by TAR using pGFCS in VL6-48B.The pGFCS-mediated TAR assembly showed a zero rate of vector recircularization and an average correct assembly yield of 79%indicating that the dual-selection strategy provides an efficient approach to optimizing TAR assembly.展开更多
Despite relative effectiveness of current hepatitis B therapies,there is still no curative agents available.The new emerging approaches hold promise to achieve cure and loss of hepatitis B surface antigen.Studies or c...Despite relative effectiveness of current hepatitis B therapies,there is still no curative agents available.The new emerging approaches hold promise to achieve cure and loss of hepatitis B surface antigen.Studies or clinical trials investigating new therapies remain small and either focus on patients with low viral load and without hepatotoxic injury or patients with hepatitis D co-infection,which makes it challenging to assess their effectiveness and side effect profile in hepatitis B population.展开更多
Bionanoparticles(BNPs),consisting of virus and virus-like assemblies,have attracted much attention in the biomedical field for their applications such as imaging and targeted drug delivery,owing to their well-defined ...Bionanoparticles(BNPs),consisting of virus and virus-like assemblies,have attracted much attention in the biomedical field for their applications such as imaging and targeted drug delivery,owing to their well-defined structures and well-controlled chemistries.BNPs-based core-shell structures provide a unique system for the investigation of biological interactions such as protein-protein and protein-carbohydrate interactions.However,it is still a challenge to prepare the BNPs-based core-shell structures.Herein,we describe(i) co-assembly method and(ii) template synthesis method in the development of polymer-BNPs core-shell structures.These two methods can be divided into three different systems.In system A,different polymers including poly(2-vinylpyridine)(P2VP),poly(4-vinylpyridine)(P4VP) and poly(ε-caprolactone)-block-poly(2-vinylpyridine)(PCL-b-P2VP) can form a raspberry-like structure with BNPs.In system B,polystyrene(PS) spheres end capped with free amine and BNPs can form a core-shell structure.In System C,layer-by-layer(LBL) method is used to prepare positive charged PS particles,which can be used as a template to form the core-shell structures with BNPs.These two methods may open a new way for preparing novel protein-based functional materials for potential applications in the biomedical field.展开更多
文摘Emerging infectious diseases are major threats to human health.Most severe viral disease outbreaks occur in developing regions where health conditions are poor.With increased international travel and business,the possibility of eventually transmitting infectious viruses between different countries is increasing.The most effective approach in preventing viral diseases is vaccination.However,vaccines are not currently available for numerous viral diseases.Viruslike particles(VLPs) are engineered vaccine candidates that have been studied for decades.VLPs are constructed by viral protein expression in various expression systems that promote the selfassembly of proteins into structures resembling virus particles.VLPs have antigenicity similar to that of the native virus,but are non-infectious as they lack key viral genetic material.VLP vaccines have attracted considerable research interest because they offer several advantages over traditional vaccines.Studies have shown that VLP vaccines can stimulate both humoral and cellular immune responses,which may offer effective antiviral protection.Here we review recent developments with VLP-based vaccines for several highly virulent emerging or re-emerging infectious diseases.The infectious agents discussed include RNA viruses from different virus families,such as the Arenaviridae,Bunyaviridae,Caliciviridae,Coronaviridae,Filoviridae,Flaviviridae,Orthomyxoviridae,Paramyxoviridae,and Togaviridae families.
文摘Ebola virus （EBOV） is a key member of Filoviridae family and causes severe human infectious diseases with high morbidity and mortality. As a typical negative-sense single-stranded RNA （-ssRNA） viruses, EBOV possess a nucleocapsid protein （NP） to facilitate genomic RNA encapsidation to form viral ribonucleoprotein complex （RNP） together with genome RNA and polymerase, which plays the most essential role in virus proliferation cycle. However, the mechanism of EBOV RNP formation remains unclear. In this work, we solved the high resolution structure of core domain of EBOV NP. The polypeptide of EBOV NP core domain （NPcore） pos- sesses an N-lobe and C-lobe to clamp a RNA binding groove, presenting similarities with the structures of the other reported viral NPs encoded by the members from Mononegavirales order. Most strikingly, a hydrophobic pocket at the surface of the C-lobe is occupied by an a- helix of EBOV NPcore itself, which is highly conserved among filoviridae family. Combined with other bio- chemical and biophysical evidences, our results provides great potential for understanding the mechanism underlying EBOV RNP formation via the mobility of EBOV NP element and enables the development of antiviral therapies targeting EBOV RNP formation.
基金supported by the Strategic Priority Research Program (XDB29010000)National Key Research and Development Program (2018YFA0900801)+5 种基金National Science Foundation Grants 32200135 and 12034006supported by National Science Fund for Distinguished Young Scholar (No.32325004)the NSFS Innovative Research Group (No.81921005)supported by the Young Elite Scientists Sponsorship Program by CAST (2022QNRC001)the Youth Innovation Promotion Association of CAS grantsupported by the Special Research Assistant Project of the Chinese Academy of Sciences.
文摘Varicella-zoster is a highly communicable virus that can be transmitted through the airborne route.About one quarter of people are infected with this virus.Previous studies have described the structure of A-capsid and a blurred reconstruction of the C-capsid with icosahedral symmetry.In this study,we have determined the more precise detailed structures of the varicella-zoster virus(VZV)B-and C-capsid in icosahedral symmetry using a combination of block-based reconstruction and symmetry relaxation strategies.In addition,we are reporting structural details of the portal vertex reconstructions in five-fold symmetry and portal reconstructions in twelve-fold symmetry.The structures unveil the basis for the high thermal stability of the VZV capsid.The conformational flexibility of structural elements of the capsid plays a role in the assembly of the capsid and drives processes critical for the viral life cycle.The results of the study open up new avenues for the development of drugs against a highly prevalent and contagious pathogen.
文摘The Phytoreovirus rice dwarf virus (RDV) has a complex nucleocapsid architecture composed of multiple proteins and RNAs. However, specific RNA-protein and protein-protein interactions involved in virion packaging have not been entirely elucidated. In order to define mechanisms governing RDV particle assembly, interactions between individual components were analyzed both in vivo and in vitro. The P7 core protein binds specifically and with high affinity to all 12 genomic RDV dsRNAs. P1, a putative RNA polymerase, P5, a putative guanyltransferase and P7 are encapsidated within the virion and also bind viral transcripts based upon in vitro binding assays. P1, P5, P7 and genomic dsRNAs were lacking in empty particles purified from infected tissues that also yielded fractions containing intact, infectious particles. In addition, P7 forms complexes with P1 and P3, a core capsid protein, in viral particles. These results indicate the possibility that core proteins and dsRNAs interact as one unit suggesting a mechanism for assortment of viral RNAs and subsequent packaging into core particles.
文摘The first appearance of lipid rafts, or lipid rafts-like structure, was occasionally observed by cryo-electronic microscopy in 1980s as cavity, such as caveolae. However, the fully understanding of lipid raft was attributed by the studies of T cell activation, virus entry/budding, and other membrane events. During the interaction of T cell and antigen presenting cell, a highly organized structure is formed at the interface of the two cells, where cholesterol and sphingolipids are enriched, and form a liquid ordered phase that facilitates the signaling proteins on and off. Lipid rafts are also involved in virus entry and assembly. In this review, we will discuss cholesterolsphingolipid floating microdomain, the lipid raft as a unique compartment of the plasma membrane, with biological functions that ensure correct intracellular traffic of proteins and lipids, such as protein-protein interactions by concentrating certain proteins in these microdomains, while excluding others. We also discuss the disruption of lipid rafts is related to different diseases and aging, and we especially exploit the lipid rafts as pharmaceutical targets for anti-virus and anti-inflammation, particularly a new approach to control HIV infection for AIDS prevention and protection by inhibition or disruption of lipid rafts. Cellular ＆ Molecular Immunology.
基金The Knowledge Innovation Program of the Chinese Academy of Sciences (KSCX2-EW-Z-3)
文摘Torque teno virus(TTV) is a nonenveloped virus containing a single-stranded,circular DNA genome of approximately 3.8kb.We completely synthesized the 3 808 nucleotides of the TTV(SANBAN isolate) genome,which contains a hairpin structure and a GC-rich region.More than 100 overlapping oligonucleotides were chemically synthesized and assembled by polymerase chain assembly reaction(PCA),and the synthesis was completed with splicing by overlap extension(SOEing).This study establishes the methodological basis of the chemical synthesis of a viral genome for use as a live attenuated vaccine or gene therapy vector.
文摘目的通过改变原噬菌体ms2包膜蛋白RNA包装位点（19碱基的茎环结构）的数量及亲和力，构建新的原核表达系统，探讨表达内含长片段（达到理论上的1900bp）RNA的耐RNase病毒样颗粒的可能性。方法首先设计含HindⅢ和NotⅠ酶切位点的引物，扩增ms2包膜蛋白的编码成熟酶蛋白和衣壳蛋白的1700bp序列，并将原来的19mer的包装位点序列改变为C-5变异体（19 bp stem-loop结构中-5位的尿嘧啶改变为胞嘧啶），HindⅢ和NotⅠ酶切后，与用同样酶切的表达载体pET-28（b）相连接，得到重组载体pET-ms2-pac。应用重叠PCR扩增3种病毒的5段嵌合体序列（包括3段SARS-CoV基因、一段HCV基因和一段H5N1基因），并在SARS-CoV3和HCV序列之间插入一个19mer的变异体包装位点序列，在设计引物时，使嵌合体两端含有NotⅠ酶切位点，与NotⅠ酶切的重组载体pET-ms2-pac相连接，构建得到具有2个变异包装位点的表达载体pET-ms2-3V。同时构建3种对照重组表达载体，分别测定N-P3V-pET-P、N-P3V-pET-C、P-3V-pET-P和pET-ms2-3 V 4种重组表达质粒表达产物的260nm吸光度（A260）值，根据公式A260=0．125mg／ml计算4种表达产物的表达效率。结果成功构建了4种原核表达载体：pET-ms2-3V、P-3V-pET-P、N-P3V-pET-P和N-P3V-pET-C。pET-ms2-3V和P-3V-pET-P经原核表达后得到含全长为1891的5段嵌合体RNA的病毒样颗粒；N-P3V-pET-P、N-P3V-pET-C其原核表达产物病毒样颗粒中仅包装了1200bp的目的嵌合体RNA。N-P3V-pET-P、N-P3V-pET-C、P-3V-pET-P和pET-ms2-3V的表达效率分别为0．23、0．35、0．35和0．51mg／ml。N-P3V-pET-C比N-P3V-pET-P表达效率高52％，而pET-ms2-3V比P-3V-pET-P表达效率高38％。所包装的RNA具有耐RNase和DNase消化的特性以及良好的不同温度条件下的稳定性。结论通过改变噬菌体ms2 RNA包装位点（19碱基的茎环结构）的数量，可构建能表达内含达到理论上的约1900bp外源RNA�
基金supported by grants from the National Natural Science Foundation of China(31172434,31372565)
文摘Viruses in the family Reoviridae are non-enveloped particles comprising a segmented double-stranded RNA genome surrounded by a two-layered or multi-layered icosahedral protein capsid.These viruses are classified into two sub-families based on their particle structural organization.Recent studies have focused on high-resolution three-dimensional structures of reovirus particles by using cryo-electron microscopy (cryo-EM) to approach the resolutions seen in X-ray crystallographic structures.The results of cryo-EM image reconstructions allow tracing of most of the protein side chains,and thus permit integration of structural and functional information into a coherent mechanism for reovirus assembly and entry.
基金supported by the National Science and Technology Major Project of China(2018ZX10711001-006)the Key Research Program of the Chinese Academy of Sciences(KJZD-SW-L06-02)。
文摘Transformation-associated recombination(TAR)has been widely used to assemble large DNA constructs.One of the significant obstacles hindering assembly efficiency is the presence of error-prone DNA repair pathways in yeast,which results in vector backbone recircularization or illegitimate recombination products.To increase TAR assembly efficiency,we prepared a dual-selective TAR vector,pGFCS,by adding a PADH1-URA3 cassette to a previously described yeast-bacteria shuttle vector,p GF,harboring a PHIS3–HIS3 cassette as a positive selection marker.This new cassette works as a negative selection marker to ensure that yeast harboring a recircularized vector cannot propagate in the presence of 5-fluoroorotic acid.To prevent pGFCS bearing ura3 from recombining with endogenous ura3-52 in the yeast genome,a highly transformable Saccharomyces cerevisiae strain,VL6-48B,was prepared by chromosomal substitution of ura3-52 with a transgene conferring resistance to blasticidin.A55-kb genomic fragment of monkeypox virus encompassing primary detection targets for quantitative PCR was assembled by TAR using pGFCS in VL6-48B.The pGFCS-mediated TAR assembly showed a zero rate of vector recircularization and an average correct assembly yield of 79%indicating that the dual-selection strategy provides an efficient approach to optimizing TAR assembly.
文摘Despite relative effectiveness of current hepatitis B therapies,there is still no curative agents available.The new emerging approaches hold promise to achieve cure and loss of hepatitis B surface antigen.Studies or clinical trials investigating new therapies remain small and either focus on patients with low viral load and without hepatotoxic injury or patients with hepatitis D co-infection,which makes it challenging to assess their effectiveness and side effect profile in hepatitis B population.
基金support from the US NSF CAREER program,US DoD (W911NF-09-1-0236),the Alfred P. Sloan Scholarship, the Camille Dreyfus Teacher Scholar Award, DoD-BCRP,and the W.M.Keck Foundation
文摘Bionanoparticles(BNPs),consisting of virus and virus-like assemblies,have attracted much attention in the biomedical field for their applications such as imaging and targeted drug delivery,owing to their well-defined structures and well-controlled chemistries.BNPs-based core-shell structures provide a unique system for the investigation of biological interactions such as protein-protein and protein-carbohydrate interactions.However,it is still a challenge to prepare the BNPs-based core-shell structures.Herein,we describe(i) co-assembly method and(ii) template synthesis method in the development of polymer-BNPs core-shell structures.These two methods can be divided into three different systems.In system A,different polymers including poly(2-vinylpyridine)(P2VP),poly(4-vinylpyridine)(P4VP) and poly(ε-caprolactone)-block-poly(2-vinylpyridine)(PCL-b-P2VP) can form a raspberry-like structure with BNPs.In system B,polystyrene(PS) spheres end capped with free amine and BNPs can form a core-shell structure.In System C,layer-by-layer(LBL) method is used to prepare positive charged PS particles,which can be used as a template to form the core-shell structures with BNPs.These two methods may open a new way for preparing novel protein-based functional materials for potential applications in the biomedical field.
