The use of fiber as a catalyst carrier to construct heterogeneous catalysts with good catalytic activity and recycling performance has received wide attention.In this study,three phenylboronic acid functionalized poly...The use of fiber as a catalyst carrier to construct heterogeneous catalysts with good catalytic activity and recycling performance has received wide attention.In this study,three phenylboronic acid functionalized polyacrylonitrile fiber(PANF)catalysts were synthesized by amination and quaternization.Fourier transform infrared spectroscopy,X-ray diffractometry,scanning electron microscopy,and X-ray photoelectron spectroscopy were used to verify the successful grafting of phenylboronic acid and the structural integrity of the fiber catalyst after recycling.The activity of the catalysts was explored with the Friedel–Crafts alkylation between indole and aromatic aldehydes.The results indicate that the synthesized catalyst(PANp-BAF)in which the phenylboronic acid functional group was linked at the para position,exhibited the highest catalytic activity for the Friedel–Crafts alkylation.The substrate scope experiments confirmed that the catalyst has outstanding catalytic activity for most aromatic aldehydes,especially for those containing moderate electron donating groups.Moreover,the catalyst can be reused eight times in water without significant decrease in its catalytic activity.Further,the scale-up experiment confirmed that the fiber catalyst has a certain potential for industrial application.展开更多
To overcome the pain and risk of hypoglycemia in insulin administration,glucose-responsive microneedles have been developed by researchers,which could release insulin according to the blood glucose level.We designed a...To overcome the pain and risk of hypoglycemia in insulin administration,glucose-responsive microneedles have been developed by researchers,which could release insulin according to the blood glucose level.We designed a kind of particles by a reversible addition-fragmentation chain transfer(RAFT)method containing a phenylboronic acid group as the sensor of glucose and carrier of insulin.poly(ethylene glycol)(PEG)-2-(dodecylthio(thiocarbonyl)thio)-2-methylpropionic acid(DDMAT)was synthesized as a macromolecular RAFT agent,which was then reacted with 3-acrylamidophenylboronic acid(AAPBA)to synthesize the block copolymer PEG-b-PAAPBA.Glucose-responsive particles loaded with insulin were prepared by self-assembly based on hydrophilic-hydrophobic interactions.Microneedle patches loaded with glucose-responsive particles were prepared using hyaluronic acid as the substrate.The insulin release behavior of the particles in glucose solutions of 0,100,and 400 mg/dL showed significant glucose responsiveness and good biosafety.The results of blood glucose control experiments in rats indicate that a single microneedle patch can effectively maintain normal blood glucose for over 7 h.展开更多
The negative ion fast atom bombardment (NIFAB) mass spectra of mono-,di-saccharides and glycosides using phenylboronic acid (PBA) as reagent have been studied.In the ion source,PBA reacts stereospecifically with the m...The negative ion fast atom bombardment (NIFAB) mass spectra of mono-,di-saccharides and glycosides using phenylboronic acid (PBA) as reagent have been studied.In the ion source,PBA reacts stereospecifically with the molecules containing cis-vicinal glycols to form characteristic ions, from which the stereo-isomers of saccharides can be definitely distinguished.Disaccharides and glyco- sides with β-glycosidic linkage seem to be unfavorabale to react with PBA,therefore,by comparison of the abundances of the characteristic ions,the configuration of the glycosidic linkage in these compounds may be inferred.展开更多
A general functionalization strategy was reported,which enables one to conjugate saccharide(SA) on gold nanoparticle(GNP) surface without affecting SA properties.First,disulfide phenylboronic acid(Bor) functiona...A general functionalization strategy was reported,which enables one to conjugate saccharide(SA) on gold nanoparticle(GNP) surface without affecting SA properties.First,disulfide phenylboronic acid(Bor) functionalized GNPs(Bor@GNPs) were synthesized by the reaction of citrate stabilized GNPs of 13 nm in diameter with the mixture of Bor and pentapeptide(Cys-Ala-Leu-Asn-Asn,CALNN).Subsequently,the SA-GNP conjugates(SA@GNPs) were prepared by coupling SA to the GNP surface via the reaction of phenylboronic acid(PBA) with the cis-diol configuration in SA.The interactions of three SA@GNPs with three lectins have been analyzed by UV-visible spectroscopic and transmission electronic microscopic(TEM) techniques,respectively.The experimental results demonstrate that SA@GNPs can efficiently bind to lectins and show a great promise as optical probes for monitoring specific affinities of lectins for SA,and detecting lectins with high sensitivity.展开更多
Despite great therapeutic effect of Abraxane®,complex preparation technology and unfavorable pharmacokinetics still restricted the clinical application of albumin-based paclitaxel(PTX)nanoparticles(NPs).Herein,we...Despite great therapeutic effect of Abraxane®,complex preparation technology and unfavorable pharmacokinetics still restricted the clinical application of albumin-based paclitaxel(PTX)nanoparticles(NPs).Herein,we reported that an albumin-binding prodrug,phenylboronic acid-conjugated PTX(P-PTX),can form the uniform NPs with the diameters around 100 nm with the help of albumin via simple one-step nano-precipitation method.The albumin-based nanomedicines were stabilized by the integration of a single boronic acid with PTX due to the increased affinity based on multiple intermolecular interactions.We found that albumin-based P-PTX NPs exhibited superior colloidal stability over albumin-based PTX NPs through one-step nanoprecipitation approach,achieving longer in vivo circulation time and higher concentration in tumor than those of the marketed Abraxane®.Furthermore,the albumin-based P-PTX NPs with great stability and enhanced intratumoral enrichment,increased the maximum tolerated dose of PTX,remarkably suppressed the growth of breast tumor and lung metastasis,prolonged survival of melanoma tumors-bearing mice.Such a convenient and effective system gains an insight into the impact of phenylboronic acid group on the albumin-based PTX NPs,provides potent strategy for the rational design of albumin-based antitumor nanomedicines.展开更多
The physical environment plays a critical role in modulating stem cell differentiation into specific lineages. In this study, we designed and synthesized a series of low-molecular-weight gels (LMWGs) with different ...The physical environment plays a critical role in modulating stem cell differentiation into specific lineages. In this study, we designed and synthesized a series of low-molecular-weight gels (LMWGs) with different moduli based on phenylboronic acid derivatives. The moduli of the LMWGs were readily tuned by varying the alkyl chain without any chemical crosslinker. The cell responses to the gels were evaluated with mesenchymal stem cell (MSCs), in respect of cell morphology, proliferation and differentiation. The prepared gels were non-toxic to MSCs, suggesting good biocompatibility. The hydrogel stiffness exerted a striking modulation effect on MSC fate decisions, where MSCs were inclined to differentiate into osteoblasts in stiff LMWGs and into chondrocytes in soft LMWGs. The pivotal elastic modulus of the LMWGs to drive MSC differentiation into osteoblastic lineage and chondrocytic lineage were approximately 20 kPa - 40 kPa and 1 kPa - 10 kPa, respectively. Overall, our results demonstrated that the modification ofhydrogel stiffness via tuning the alkyl chain was a simple but effective approach to regulate MSC differentiation into specific lineage, which might have important implications in the design of LMWGs for tissue engineering applications.展开更多
Interleukin 2 (IL-2) is widely used as an active immunotherapeutic agent in clinical metastatic cancers. However, its therapeutic concentrations do not last long due to its short half-life. Thus, only a transient prol...Interleukin 2 (IL-2) is widely used as an active immunotherapeutic agent in clinical metastatic cancers. However, its therapeutic concentrations do not last long due to its short half-life. Thus, only a transient proliferation of the anti-cancer CD8+ T cells can be achieved, resulting in poor efficacy. Therefore, the aim of this work was to create a system that promotes CD8+ T cell proliferation at the tumor site using IL-2 persistently present and activates an anti-cancer immune response. This goal was achieved by the design of the IL-2-loaded polypeptide nanoparticles (P-IL-2) where methoxy poly(ethylene glycol) block poly-[(N-2-hydroxyethyl)-aspartamide] phenylboronic acid was used to encapsulate IL-2 through boron-nitrogen coordination with poly(L-lysine). P-IL-2 significantly prolonged the circulation time of IL-2 and achieved a selective drug release at the tumor site in the presence of high levels of reactive oxygen species, thus activating an anti-cancer immune response and exerting a better anti-cancer effect. The half-life of P-IL-2 was 3.15-fold higher than that of IL-2, and the quantity of CD8+ T cells after using P-IL-2 was 1.89-fold higher than that after using IL-2. In addition, the combination of P-IL-2 and anti-CTLA-4 monoclonal antibody resulted in an enhanced immune activation. Hence, this work provides a new approach to improve the efficacy of IL-2 in anti-cancer immunotherapy.展开更多
N-Arylation of a wide variety of amines with phenylboronic acid catalyzed by copper acetate under 20%aqueous solution of n-Bu_4NOH was accomplished in good to excellent yields(up to 92%) and substrate conversions(u...N-Arylation of a wide variety of amines with phenylboronic acid catalyzed by copper acetate under 20%aqueous solution of n-Bu_4NOH was accomplished in good to excellent yields(up to 92%) and substrate conversions(up to 96%).展开更多
Due to the formation of dynamic boronate ester bonds between phenylboronic acid(PBA) and 1,2-and 1,3-diols, PBAcontaining biomaterials show increasing applications in biomedical areas, including responsive nanobiomate...Due to the formation of dynamic boronate ester bonds between phenylboronic acid(PBA) and 1,2-and 1,3-diols, PBAcontaining biomaterials show increasing applications in biomedical areas, including responsive nanobiomaterials for targeting delivery of chemical drugs, protein drugs, gene drugs and imaging agents in vitro and in vivo for detection of various bioactive molecules such as sialic acid, saccharides, adenosine triphosphate(ATP) and dopamine. With the specific reaction between PBA and sialic acid, which is overexpressed in many kinds of cancer cells, PBA has been used as a targeting moiety for tumortargeting drug delivery. Additionally, PBA as an electron acceptor affords nanomaterials Lewis acid-base coordination with electron donor atoms such as nitrogen and oxygen, which can be exploited for developing drug delivery systems with high drug loading. Furthermore, PBA-containing materials can stoichiometric consume reactive oxygen species(ROS) and show a nucleus targeting ability. This current review outlined PBA-containing biomaterials with various responsive abilities including sialic acid-targeting, sugars-binding, ROS-response, ATP-response, dopamine-binding, and nuclear targeting. On this basis, their biomedical applications were summarized.展开更多
Uveitis is a sophisticated syndrome showing a high relevance with reactive oxygen species(ROS).Herein,an ROS-responsive PEGylated polypeptide based macromolecular prodrug of herbaceous antioxidant ethyl caffeate(EC)is...Uveitis is a sophisticated syndrome showing a high relevance with reactive oxygen species(ROS).Herein,an ROS-responsive PEGylated polypeptide based macromolecular prodrug of herbaceous antioxidant ethyl caffeate(EC)is designed via phenylboronic esters with improved solubility for the alleviation of uveitis.The antioxidative 4-hydroxybenzyl alcohol(HBA)and EC can be released from the macromolecular EC prodrug under the stimulation of ROS,which can effectively protect cells against oxidative stress-induced injury in an ROS-depletion way.The antioxidative and protective effects of the macromolecular EC prodrug in vivo are further verified in a uveitis mouse model.Overall,this work not only provides a handy method to synthesize a phenylboronic ester-bearing EC prodrug which is highly sensitive to pathological ROS,but also depicts a promising future to apply macromolecular antioxidative prodrugs in the treatment of uveitis as well as other ROS-related diseases.展开更多
基金financially supported by the National Natural Science Foundation of China(21777111)。
文摘The use of fiber as a catalyst carrier to construct heterogeneous catalysts with good catalytic activity and recycling performance has received wide attention.In this study,three phenylboronic acid functionalized polyacrylonitrile fiber(PANF)catalysts were synthesized by amination and quaternization.Fourier transform infrared spectroscopy,X-ray diffractometry,scanning electron microscopy,and X-ray photoelectron spectroscopy were used to verify the successful grafting of phenylboronic acid and the structural integrity of the fiber catalyst after recycling.The activity of the catalysts was explored with the Friedel–Crafts alkylation between indole and aromatic aldehydes.The results indicate that the synthesized catalyst(PANp-BAF)in which the phenylboronic acid functional group was linked at the para position,exhibited the highest catalytic activity for the Friedel–Crafts alkylation.The substrate scope experiments confirmed that the catalyst has outstanding catalytic activity for most aromatic aldehydes,especially for those containing moderate electron donating groups.Moreover,the catalyst can be reused eight times in water without significant decrease in its catalytic activity.Further,the scale-up experiment confirmed that the fiber catalyst has a certain potential for industrial application.
基金supported by the Natural Science Foundation of Zhejiang Province(No.LHDMZ22H300003)the Science and Technology Program of Zhejiang Province(No.2019C03063),China。
文摘To overcome the pain and risk of hypoglycemia in insulin administration,glucose-responsive microneedles have been developed by researchers,which could release insulin according to the blood glucose level.We designed a kind of particles by a reversible addition-fragmentation chain transfer(RAFT)method containing a phenylboronic acid group as the sensor of glucose and carrier of insulin.poly(ethylene glycol)(PEG)-2-(dodecylthio(thiocarbonyl)thio)-2-methylpropionic acid(DDMAT)was synthesized as a macromolecular RAFT agent,which was then reacted with 3-acrylamidophenylboronic acid(AAPBA)to synthesize the block copolymer PEG-b-PAAPBA.Glucose-responsive particles loaded with insulin were prepared by self-assembly based on hydrophilic-hydrophobic interactions.Microneedle patches loaded with glucose-responsive particles were prepared using hyaluronic acid as the substrate.The insulin release behavior of the particles in glucose solutions of 0,100,and 400 mg/dL showed significant glucose responsiveness and good biosafety.The results of blood glucose control experiments in rats indicate that a single microneedle patch can effectively maintain normal blood glucose for over 7 h.
文摘The negative ion fast atom bombardment (NIFAB) mass spectra of mono-,di-saccharides and glycosides using phenylboronic acid (PBA) as reagent have been studied.In the ion source,PBA reacts stereospecifically with the molecules containing cis-vicinal glycols to form characteristic ions, from which the stereo-isomers of saccharides can be definitely distinguished.Disaccharides and glyco- sides with β-glycosidic linkage seem to be unfavorabale to react with PBA,therefore,by comparison of the abundances of the characteristic ions,the configuration of the glycosidic linkage in these compounds may be inferred.
基金Supported by the National Basic Research Program of China(No.2011CB935800)the Project of the Jilin Provincial Science and Technology Department,China(No.20100701)
文摘A general functionalization strategy was reported,which enables one to conjugate saccharide(SA) on gold nanoparticle(GNP) surface without affecting SA properties.First,disulfide phenylboronic acid(Bor) functionalized GNPs(Bor@GNPs) were synthesized by the reaction of citrate stabilized GNPs of 13 nm in diameter with the mixture of Bor and pentapeptide(Cys-Ala-Leu-Asn-Asn,CALNN).Subsequently,the SA-GNP conjugates(SA@GNPs) were prepared by coupling SA to the GNP surface via the reaction of phenylboronic acid(PBA) with the cis-diol configuration in SA.The interactions of three SA@GNPs with three lectins have been analyzed by UV-visible spectroscopic and transmission electronic microscopic(TEM) techniques,respectively.The experimental results demonstrate that SA@GNPs can efficiently bind to lectins and show a great promise as optical probes for monitoring specific affinities of lectins for SA,and detecting lectins with high sensitivity.
基金the National Key Research and Development Program of China(No.2021YFA0909900)the National Natural Science Foundation of China(Nos.82073777 and 81803442)+1 种基金the General Project of Liaoning Provincial Department of Education(Nos.LJKZ0927 and LJKQZ2021034)the Natural Science Foundation of Liaoning Province(No.2022-BS-157).
文摘Despite great therapeutic effect of Abraxane®,complex preparation technology and unfavorable pharmacokinetics still restricted the clinical application of albumin-based paclitaxel(PTX)nanoparticles(NPs).Herein,we reported that an albumin-binding prodrug,phenylboronic acid-conjugated PTX(P-PTX),can form the uniform NPs with the diameters around 100 nm with the help of albumin via simple one-step nano-precipitation method.The albumin-based nanomedicines were stabilized by the integration of a single boronic acid with PTX due to the increased affinity based on multiple intermolecular interactions.We found that albumin-based P-PTX NPs exhibited superior colloidal stability over albumin-based PTX NPs through one-step nanoprecipitation approach,achieving longer in vivo circulation time and higher concentration in tumor than those of the marketed Abraxane®.Furthermore,the albumin-based P-PTX NPs with great stability and enhanced intratumoral enrichment,increased the maximum tolerated dose of PTX,remarkably suppressed the growth of breast tumor and lung metastasis,prolonged survival of melanoma tumors-bearing mice.Such a convenient and effective system gains an insight into the impact of phenylboronic acid group on the albumin-based PTX NPs,provides potent strategy for the rational design of albumin-based antitumor nanomedicines.
基金This work was supported by the Natural Science Foundation grants (Nos. 31600765 and 21672164), Natural Science Foundation of Zhejiang Province (No.LY 15B020001), Sichuan Province Miaozi Project (No. 2016RZ0032), and Chinese Postdoctoral Science Foundation (2016M062690).
文摘The physical environment plays a critical role in modulating stem cell differentiation into specific lineages. In this study, we designed and synthesized a series of low-molecular-weight gels (LMWGs) with different moduli based on phenylboronic acid derivatives. The moduli of the LMWGs were readily tuned by varying the alkyl chain without any chemical crosslinker. The cell responses to the gels were evaluated with mesenchymal stem cell (MSCs), in respect of cell morphology, proliferation and differentiation. The prepared gels were non-toxic to MSCs, suggesting good biocompatibility. The hydrogel stiffness exerted a striking modulation effect on MSC fate decisions, where MSCs were inclined to differentiate into osteoblasts in stiff LMWGs and into chondrocytes in soft LMWGs. The pivotal elastic modulus of the LMWGs to drive MSC differentiation into osteoblastic lineage and chondrocytic lineage were approximately 20 kPa - 40 kPa and 1 kPa - 10 kPa, respectively. Overall, our results demonstrated that the modification ofhydrogel stiffness via tuning the alkyl chain was a simple but effective approach to regulate MSC differentiation into specific lineage, which might have important implications in the design of LMWGs for tissue engineering applications.
基金supported by the National Natural Science Foundation of China(Nos.52025035,51873206 and 52203198)the Project of Health research talents Project of Jilin Province(No.2020SCZ06)+1 种基金the Project of Jilin Province Development and Reform Commission(No.2021C043-6)the Jilin Provincial International Cooperation Key Laboratory of Biomedical Polymers(No.20210504001GH).
文摘Interleukin 2 (IL-2) is widely used as an active immunotherapeutic agent in clinical metastatic cancers. However, its therapeutic concentrations do not last long due to its short half-life. Thus, only a transient proliferation of the anti-cancer CD8+ T cells can be achieved, resulting in poor efficacy. Therefore, the aim of this work was to create a system that promotes CD8+ T cell proliferation at the tumor site using IL-2 persistently present and activates an anti-cancer immune response. This goal was achieved by the design of the IL-2-loaded polypeptide nanoparticles (P-IL-2) where methoxy poly(ethylene glycol) block poly-[(N-2-hydroxyethyl)-aspartamide] phenylboronic acid was used to encapsulate IL-2 through boron-nitrogen coordination with poly(L-lysine). P-IL-2 significantly prolonged the circulation time of IL-2 and achieved a selective drug release at the tumor site in the presence of high levels of reactive oxygen species, thus activating an anti-cancer immune response and exerting a better anti-cancer effect. The half-life of P-IL-2 was 3.15-fold higher than that of IL-2, and the quantity of CD8+ T cells after using P-IL-2 was 1.89-fold higher than that after using IL-2. In addition, the combination of P-IL-2 and anti-CTLA-4 monoclonal antibody resulted in an enhanced immune activation. Hence, this work provides a new approach to improve the efficacy of IL-2 in anti-cancer immunotherapy.
文摘N-Arylation of a wide variety of amines with phenylboronic acid catalyzed by copper acetate under 20%aqueous solution of n-Bu_4NOH was accomplished in good to excellent yields(up to 92%) and substrate conversions(up to 96%).
基金supported by the National Key Research and Development Program of China(2017YFA0701301,2017YFA0205400)the National Natural Science Foundation of China(51690153,21720102005,51803089)the Program for Changjiang Scholars and Innovative Research Team in University,the Fundamental Research Funds for the Central Universities。
文摘Due to the formation of dynamic boronate ester bonds between phenylboronic acid(PBA) and 1,2-and 1,3-diols, PBAcontaining biomaterials show increasing applications in biomedical areas, including responsive nanobiomaterials for targeting delivery of chemical drugs, protein drugs, gene drugs and imaging agents in vitro and in vivo for detection of various bioactive molecules such as sialic acid, saccharides, adenosine triphosphate(ATP) and dopamine. With the specific reaction between PBA and sialic acid, which is overexpressed in many kinds of cancer cells, PBA has been used as a targeting moiety for tumortargeting drug delivery. Additionally, PBA as an electron acceptor affords nanomaterials Lewis acid-base coordination with electron donor atoms such as nitrogen and oxygen, which can be exploited for developing drug delivery systems with high drug loading. Furthermore, PBA-containing materials can stoichiometric consume reactive oxygen species(ROS) and show a nucleus targeting ability. This current review outlined PBA-containing biomaterials with various responsive abilities including sialic acid-targeting, sugars-binding, ROS-response, ATP-response, dopamine-binding, and nuclear targeting. On this basis, their biomedical applications were summarized.
基金financially supported by National Key Research and Development Project (No. 2020YFE0204400)
文摘Uveitis is a sophisticated syndrome showing a high relevance with reactive oxygen species(ROS).Herein,an ROS-responsive PEGylated polypeptide based macromolecular prodrug of herbaceous antioxidant ethyl caffeate(EC)is designed via phenylboronic esters with improved solubility for the alleviation of uveitis.The antioxidative 4-hydroxybenzyl alcohol(HBA)and EC can be released from the macromolecular EC prodrug under the stimulation of ROS,which can effectively protect cells against oxidative stress-induced injury in an ROS-depletion way.The antioxidative and protective effects of the macromolecular EC prodrug in vivo are further verified in a uveitis mouse model.Overall,this work not only provides a handy method to synthesize a phenylboronic ester-bearing EC prodrug which is highly sensitive to pathological ROS,but also depicts a promising future to apply macromolecular antioxidative prodrugs in the treatment of uveitis as well as other ROS-related diseases.