Two supramolecular organic frameworks(SOFs)have been constructed from the co-assembly of biimidazolium-derived octacationic components and cucurbit[8]uril in water.Dynamic light scattering and ^(1)H NMR experiments re...Two supramolecular organic frameworks(SOFs)have been constructed from the co-assembly of biimidazolium-derived octacationic components and cucurbit[8]uril in water.Dynamic light scattering and ^(1)H NMR experiments reveal that both SOFs can undergo reversible assembly and disassembly at room temperature.One of the SOFs displays unprecedently high maximum tolerated dose of 120 mg/kg with mice,which improves by 40%compared with the highest value of the reported SOFs.In vitro and in vivo tests show that the SOF can adsorb doxorubicin and overcome the resistance of multidrugresistant MDR A549/ADR tumor cells to realize intracellular delivery,leading to enhanced antitumor efficacy.Moreover,it can also completely inhibit the posttreatment phototoxicity of photofrin and fully neutralize the anticoagulation of both unfractionated heparin and low molecular weight heparins through efficient inclusion and elimination or sequestration mechanism.As the first examples that undergo roomtemperature reversible assembly and disassembly,the new SOFs in principle allow for quantitative analysis of the molecular components in the body that is prerequisite for preclinical evaluation in the future.展开更多
Neodymium selenide nanoparticles were synthesized and surface-modified usingβ-cyclodextrin-citrate to control agglomeration and achieve the desired particle size.The nanoparticles were characterized by various techni...Neodymium selenide nanoparticles were synthesized and surface-modified usingβ-cyclodextrin-citrate to control agglomeration and achieve the desired particle size.The nanoparticles were characterized by various techniques,including X-ray diffraction,transmission electron microscopy(TEM),and X-ray photoelectron spectroscopy(XPS).XRD results reveal high crystallinity,with characteristic peaks corresponding to Nd_(2)Se_(3),while TEM analysis shows rod-shaped nanoparticles with an average size of~55 nm.The presence of neodymium and selenium in the+3 oxidation state was confirmed by XPS.Thermogravimetric analysis indicates that theβ-cyclodextrin-citrate coating accounts for approximately30%of the nanoparticle mass and remains stable up to 800℃.The optical properties of the nanoparticles were studied using UV-Vis-NIR spectroscopy,revealing broad absorption in the UV and NIR regions.Magnetic characterization shows soft ferromagnetic behavior,with a saturation magnetization value of0.20 emu/g.The nanoparticles were used for controlled release of 5-fluorouracil,exhibiting a pHsensitive release profile.Studies on MCF-7 cells demonstrate that 5-fluorouracil-loade d nanoparticles enhance cytotoxicity,reactive oxygen species generation,and apoptosis compared to bare nanoparticles.The IC_(50) value of(13.78±1.24)μg/mL indicates a significantly high cytotoxic activity of the drug-loaded nanoparticles against breast cancer cell lines.These findings suggest that the nanoparticles are a promising drug delivery system for enhanced cancer treatment,combining the controlled drug release with targeted cellular effects.展开更多
Multiresponsive hydrogels,capable of responding to more than one external stimulus,have demonstrated great utility in biomedical applications.This study presents a facile method for preparing an injectable,dual redox/...Multiresponsive hydrogels,capable of responding to more than one external stimulus,have demonstrated great utility in biomedical applications.This study presents a facile method for preparing an injectable,dual redox/p H-responsive hydrogel system based on poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate)(PEDOT:PSS)for the controlled delivery of pharmacologically active bevacizumab(BEV).The hydrogel system was fabricated via a one-step physical crosslinking process by mixing PEDOT:PSS with BEV,leveraging electrostatic interactions,hydrogen bonding,and ionic crosslinking.The resulting PEDOT@BEV system exhibited a homogeneously porous structure,robust mechanical stability,and good biocompatibility.Under acidic(p H=5)or alkaline(p H=10)conditions,especially when coupled with elevated reactive oxygen species(ROS)levels,the as-prepared PEDOT@BEV achieved rapid BEV release.This may be attributed to PEDOT oxidation and charge repulsion.In contrast,BEV release remained stable under physiological conditions(p H=7.4,0 mmol/L H_(2)O_(2)).In vitro results supported that the resulting PEDOT@BEV demonstrated potent anti-angiogenic efficacy,significantly inhibiting cellular migration and tube formation of human retinal vascular endothelial cells(HRVECs).The vascular endothelial growth factor expression was further reduced.In a mouse model of corneal neovascularization,the PEDOT@BEV system enabled the continuous controlled release of BEV for over 14 days.It exhibited superior anti-angiogenic efficacy compared to free BEV treatment,more effectively reducing neovascularization and corneal inflammation.The designed platform in this work demonstrated versatility by successfully incorporating other therapeutic antibodies(e.g.,rituximab,trastuzumab),highlighting its potential for tailored drug delivery in oncology and neovascular diseases.The outcome of this study offers a promising strategy for spatiotemporally controlled drug release in response to specific microenvironmental cues.展开更多
Constructing nanofibers with specific therapeutic effects against cancer is a challenge.Here,we present the synthesis approach and application prospects of supramolecular nanofibers,which are based on cucurbit[8]uril(...Constructing nanofibers with specific therapeutic effects against cancer is a challenge.Here,we present the synthesis approach and application prospects of supramolecular nanofibers,which are based on cucurbit[8]uril(CB[8])as the host and terpyridine lanthanum ions metal complex as the vip,constructed by layer-by-layer self-assembly through supramolecular interaction.Moreover,nanofibers with lanthanide luminescence properties exhibit surprising pH-responsive deformation properties and antibacterial behavior.In the tumor micro-environment,the dramatic reduction in the size of the nanofibers enables specific and hierarchical release of anticancer drugs in tumor cells to exert an advanced therapeutic effect.In addition,the synergistic therapeutic efficacy was achieved by reducing the excess of Gram-positive and Gram-negative bacteria surrounding tumor cells.The novel supramolecular nanofibers with sequential drug release and combined therapeutic mode provide new guidance for the synthesis of drug carrier materials and direction for the promotion of nanomaterial-mediated cancer therapy.展开更多
文章以生物不对称还原2-氯-1-(3,4-二氟苯基)乙酮为模型反应,探索合成抗凝血药替格瑞洛关键手性中间体的绿色工艺。通过基因挖掘得到酶CPY,构建重组菌E.coli/p ET-28a(+)-CPY,确定其最佳诱导条件为37℃,培养至对数中期(约3 h),加0.1 m M...文章以生物不对称还原2-氯-1-(3,4-二氟苯基)乙酮为模型反应,探索合成抗凝血药替格瑞洛关键手性中间体的绿色工艺。通过基因挖掘得到酶CPY,构建重组菌E.coli/p ET-28a(+)-CPY,确定其最佳诱导条件为37℃,培养至对数中期(约3 h),加0.1 m M IPTG,30℃诱导8 h。优化催化条件后,最佳反应体系为20%(V/V)异丙醇、420 m M底物浓度、16.5 g/L菌体湿重,p H=7.4,25℃反应30 h,产物产率>90%,ee值达99.9%。展开更多
基金the National Natural Science Foundation of China(No.21921003 for Z.T.L.and 22201293 for S.B.Y.)Shanghai Sailing Program(No.22YF1458300 for S.B.Y.)for financial support。
文摘Two supramolecular organic frameworks(SOFs)have been constructed from the co-assembly of biimidazolium-derived octacationic components and cucurbit[8]uril in water.Dynamic light scattering and ^(1)H NMR experiments reveal that both SOFs can undergo reversible assembly and disassembly at room temperature.One of the SOFs displays unprecedently high maximum tolerated dose of 120 mg/kg with mice,which improves by 40%compared with the highest value of the reported SOFs.In vitro and in vivo tests show that the SOF can adsorb doxorubicin and overcome the resistance of multidrugresistant MDR A549/ADR tumor cells to realize intracellular delivery,leading to enhanced antitumor efficacy.Moreover,it can also completely inhibit the posttreatment phototoxicity of photofrin and fully neutralize the anticoagulation of both unfractionated heparin and low molecular weight heparins through efficient inclusion and elimination or sequestration mechanism.As the first examples that undergo roomtemperature reversible assembly and disassembly,the new SOFs in principle allow for quantitative analysis of the molecular components in the body that is prerequisite for preclinical evaluation in the future.
文摘Neodymium selenide nanoparticles were synthesized and surface-modified usingβ-cyclodextrin-citrate to control agglomeration and achieve the desired particle size.The nanoparticles were characterized by various techniques,including X-ray diffraction,transmission electron microscopy(TEM),and X-ray photoelectron spectroscopy(XPS).XRD results reveal high crystallinity,with characteristic peaks corresponding to Nd_(2)Se_(3),while TEM analysis shows rod-shaped nanoparticles with an average size of~55 nm.The presence of neodymium and selenium in the+3 oxidation state was confirmed by XPS.Thermogravimetric analysis indicates that theβ-cyclodextrin-citrate coating accounts for approximately30%of the nanoparticle mass and remains stable up to 800℃.The optical properties of the nanoparticles were studied using UV-Vis-NIR spectroscopy,revealing broad absorption in the UV and NIR regions.Magnetic characterization shows soft ferromagnetic behavior,with a saturation magnetization value of0.20 emu/g.The nanoparticles were used for controlled release of 5-fluorouracil,exhibiting a pHsensitive release profile.Studies on MCF-7 cells demonstrate that 5-fluorouracil-loade d nanoparticles enhance cytotoxicity,reactive oxygen species generation,and apoptosis compared to bare nanoparticles.The IC_(50) value of(13.78±1.24)μg/mL indicates a significantly high cytotoxic activity of the drug-loaded nanoparticles against breast cancer cell lines.These findings suggest that the nanoparticles are a promising drug delivery system for enhanced cancer treatment,combining the controlled drug release with targeted cellular effects.
基金supported by the National Natural Science Foundation of China(Nos.82502583 and U20A20338)Huadong Medicine Joint Funds of Natural Science Foundation of Zhejiang Province(No.LHDMY23H070004)the Summit Advancement Disciplines of Zhejiang Province(Wenzhou Medical University-Pharmaceutics)。
文摘Multiresponsive hydrogels,capable of responding to more than one external stimulus,have demonstrated great utility in biomedical applications.This study presents a facile method for preparing an injectable,dual redox/p H-responsive hydrogel system based on poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate)(PEDOT:PSS)for the controlled delivery of pharmacologically active bevacizumab(BEV).The hydrogel system was fabricated via a one-step physical crosslinking process by mixing PEDOT:PSS with BEV,leveraging electrostatic interactions,hydrogen bonding,and ionic crosslinking.The resulting PEDOT@BEV system exhibited a homogeneously porous structure,robust mechanical stability,and good biocompatibility.Under acidic(p H=5)or alkaline(p H=10)conditions,especially when coupled with elevated reactive oxygen species(ROS)levels,the as-prepared PEDOT@BEV achieved rapid BEV release.This may be attributed to PEDOT oxidation and charge repulsion.In contrast,BEV release remained stable under physiological conditions(p H=7.4,0 mmol/L H_(2)O_(2)).In vitro results supported that the resulting PEDOT@BEV demonstrated potent anti-angiogenic efficacy,significantly inhibiting cellular migration and tube formation of human retinal vascular endothelial cells(HRVECs).The vascular endothelial growth factor expression was further reduced.In a mouse model of corneal neovascularization,the PEDOT@BEV system enabled the continuous controlled release of BEV for over 14 days.It exhibited superior anti-angiogenic efficacy compared to free BEV treatment,more effectively reducing neovascularization and corneal inflammation.The designed platform in this work demonstrated versatility by successfully incorporating other therapeutic antibodies(e.g.,rituximab,trastuzumab),highlighting its potential for tailored drug delivery in oncology and neovascular diseases.The outcome of this study offers a promising strategy for spatiotemporally controlled drug release in response to specific microenvironmental cues.
基金supported by the National Natural Science Foundation of China(No.82273919)Natural Science Foundation of Heilongjiang Province(No.LH2024H013)China Postdoctoral Science Foundation(No.2022MD723781).
文摘Constructing nanofibers with specific therapeutic effects against cancer is a challenge.Here,we present the synthesis approach and application prospects of supramolecular nanofibers,which are based on cucurbit[8]uril(CB[8])as the host and terpyridine lanthanum ions metal complex as the vip,constructed by layer-by-layer self-assembly through supramolecular interaction.Moreover,nanofibers with lanthanide luminescence properties exhibit surprising pH-responsive deformation properties and antibacterial behavior.In the tumor micro-environment,the dramatic reduction in the size of the nanofibers enables specific and hierarchical release of anticancer drugs in tumor cells to exert an advanced therapeutic effect.In addition,the synergistic therapeutic efficacy was achieved by reducing the excess of Gram-positive and Gram-negative bacteria surrounding tumor cells.The novel supramolecular nanofibers with sequential drug release and combined therapeutic mode provide new guidance for the synthesis of drug carrier materials and direction for the promotion of nanomaterial-mediated cancer therapy.
文摘文章以生物不对称还原2-氯-1-(3,4-二氟苯基)乙酮为模型反应,探索合成抗凝血药替格瑞洛关键手性中间体的绿色工艺。通过基因挖掘得到酶CPY,构建重组菌E.coli/p ET-28a(+)-CPY,确定其最佳诱导条件为37℃,培养至对数中期(约3 h),加0.1 m M IPTG,30℃诱导8 h。优化催化条件后,最佳反应体系为20%(V/V)异丙醇、420 m M底物浓度、16.5 g/L菌体湿重,p H=7.4,25℃反应30 h,产物产率>90%,ee值达99.9%。
