Molecular self-assembly is crucially fundamental to nature.However,the aqueous self-assembly of polymers is still a challenge.To achieve self-assembly of block copolymers [(polyacrylic acid-block-polyethylene glycol-b...Molecular self-assembly is crucially fundamental to nature.However,the aqueous self-assembly of polymers is still a challenge.To achieve self-assembly of block copolymers [(polyacrylic acid-block-polyethylene glycol-block-polyacrylic acid(PAA68-b-PEG86-b-PAA68)] in an aqueous phase,manganese oxide(MnO2) is first generated to drive phase separation of the PAA block to form the PAA68-b-PEG68-b-PAA68/MnO2 polymeric assembly that exhibits a stable structure in a physiological medium.The polymeric assembly exhibits vesicular morphology with a diameter of approximately 30 nm and high doxorubicin(DOX) loading capacity of approximately 94%.The transformation from MnO2 to Mn2+caused by endogenous glutathione(GSH)facilitates the disassembly of PAA68-b-PEG68-b-PAA68/MnO2 to enable its drug delivery at the tumor sites.The toxicity of DOXloaded PAA68-b-PEG68-b-PAA69/MnO2 to tumor cells has been verified in vitro and in vivo.Notably,drug-loaded polymeric vesicles have been demonstrated,especially in in vivo studies,to overcome the cardiotoxicity of DOX.We expect this work to encourage the potential application of polymer self-assembly.展开更多
Combination therapy such as photothermal therapy(PTT)enhanced chemotherapy is regarded as a promising strategy for cancer treatment.Herein,we developed redox-responsive polymeric vesicles based on the amphiphilic trib...Combination therapy such as photothermal therapy(PTT)enhanced chemotherapy is regarded as a promising strategy for cancer treatment.Herein,we developed redox-responsive polymeric vesicles based on the amphiphilic triblock copolymer PCL-ss-PEG-ss-PCL.To avoid the limited therapeutic effect of chemotherapeutic drugs caused by systemic exposures and drug resistance,the redox-sensitive polymeric vesicles were cargoed with two chemotherapeutics:doxorubicin(DOX)and paclitaxel(PTX).Besides,indocyanine green(ICG)was encapsulated,and cell-penetrating peptides and LHRH targeting molecule were modified on the surface of polymeric vesicles.The results indicated that the polymeric vesicles can load different kinds of drugs with high drug loading content,trigger drug release in responsive to the reductive environment,realize high cellular uptake via dual peptides and laser irradiation,and achieve higher cytotoxicity via chemo-photothermal combination therapy.Hence,the redox-responsive LHRH/TAT dual peptides-conjugated PTX/DOX/ICG co-loaded polymeric micelles exhibited great potential in tumor-targeting and chemo-photothermal therapy.展开更多
A series of triblock copolymers, containing a CO_2-switchable block poly（2-（dimethylamino）ethyl methacrylate）（PDM） block and two symmetrical hydrophilic blocks polyacrylamide（PAM）, were synthesized using atom ...A series of triblock copolymers, containing a CO_2-switchable block poly（2-（dimethylamino）ethyl methacrylate）（PDM） block and two symmetrical hydrophilic blocks polyacrylamide（PAM）, were synthesized using atom transfer radical polymerization（ATRP） method. The p H and conductivity tests showed that the triblock copolymer exhibited switchable responsiveness to CO_2, i.e. a relatively low conductivity of solution could be switched on and off by bubbling and removing of CO_2, and the triblock copolymer aqueous solution displayed a CO_2-switchable viscosity variation. The changes were all attributed to protonation of tertiary amine groups in PDM blocks and proven by 1 H-NMR. Cryogenic transmission electron microscopy and dynamic light scattering characterization demonstrated that the viscosity variation was the result of a unilamellar vesicle-network aggregate structure transition. The release of rhodamine B from the vesicles with and without CO_2 stimuli showed the potential application in drug delivery domains; after CO_2 bubbling, the drug release rate could be accelerated. Finally, reasonable mechanism of CO_2-switchable morphology changes and CO_2-induced drug release was proposed.展开更多
Comprehensive Summary The size and size distribution of polymeric nanoparticles have great impact on their physicochemical and biological properties.Polymerization-induced self-assembly(PISA)has been demonstrated to b...Comprehensive Summary The size and size distribution of polymeric nanoparticles have great impact on their physicochemical and biological properties.Polymerization-induced self-assembly(PISA)has been demonstrated to be an efficient method to fabricate various polymeric nanoparticles,among which polymeric vesicles have attracted great interest due to their unique hollow structure.展开更多
To understand and control the interfacial properties of polydiacetylenes(PDAs)vesicles withπ-conjugated backbone is very important for their colorimetric sensing of chemical and biological targets.In this work,we ado...To understand and control the interfacial properties of polydiacetylenes(PDAs)vesicles withπ-conjugated backbone is very important for their colorimetric sensing of chemical and biological targets.In this work,we adopted 10,12-pentacosadiynoic acid(PCDA)as the model molecule to prepare PDAs vesicles in aqueous solution with different forms(from monomer to blue-to-purple-to-red phase)by controlling the UV irradiation dose.The variations of the interfacial conformation of PDAs vesicles during chromatic transitions were inspected by the adsorption behaviors of probe molecules(4-(4-diethylaminostyry)-1-methylpyridinium iodide,D289)on vesicle surface with surface-specific second harmonic generation(SHG)and zeta potential measurements.Resonant SHG signal from D289 adsorbed on vesicle surface attenuated sharply,and the adsorption free energy as well as the corresponding two-photon fluorescence signal decreased slightly in chromatic transitions.While,the change in the surface density of the adsorbed D289 molecules for PDAs vesicles with different forms was relatively small as estimated from zeta potential measurements.The attenuation of the SHG intensity was thus attributed to the overall order-disorder transition and the changed orientation of D289 molecules caused by the gradual distortion of carboxyl head group driven by backbone perturbation.展开更多
α-Eleostearic acid and β-eleostearic acid formed vesicles in aqueous medium when an ethanol solution of eleostearic acid was injected rapidly into a vigorously vortexed aqueous phase. Formation of the vesicles was d...α-Eleostearic acid and β-eleostearic acid formed vesicles in aqueous medium when an ethanol solution of eleostearic acid was injected rapidly into a vigorously vortexed aqueous phase. Formation of the vesicles was demonstrated by electron microscopic observation and bromothymol blue encapsulation experiments. Polymerizations of the eleostearic acids in the formed vesicles carried out by UV irradiation produced poly-α-eleostearic acid and poly-β-eleostearic acid vesicles.展开更多
A cup shape is a dynamic morphology of cells and organelles. With the aim of elucidating the formation of the biotic cup-shaped morphology, this study investigated cup-shaped vesicles consisting of an amphiphilic dibl...A cup shape is a dynamic morphology of cells and organelles. With the aim of elucidating the formation of the biotic cup-shaped morphology, this study investigated cup-shaped vesicles consisting of an amphiphilic diblock copolymer from the aspect of synthetic polymer chemistry. Cup-shaped vesicles were obtained by the polymerization-induced self-assembly of poly(methacrylic acid)-block-poly(n-butyl methacrylate-random-methacrylic acid), PMAA-b-P(BMA-r-MAA), in an aqueous methanol solution using the photo nitroxide-mediated controlled/living radical polymerization technique. Field emission scanning electron microscopic observations demonstrated that the cup-shaped vesicles were suddenly formed during the late stage of the polymerization due to the extension of the hydrophobic P(BMA-r-MAA) block chain. During the early stage, the polymerization produced spherical vesicles rather than a cup shape. As the hydrophobic block chain was extended by the polymerization progress, the spherical vesicles reduced the size and were accompanied by the generation of small particles that were attached to the vesicles. The vesicles continued to reduce the size due to further extension of the hydrophobic chain;however, they suddenly grew into cup-shaped vesicles. This growth was accounted for by a change in the critical packing shape of the copolymer due to the hydrophobic chain extension. These findings are helpful for a better understanding of the biotic cup-shaped vesicle formation.展开更多
This work reports a SO2 derivative-detecting and colorful hyperbranched polymeric ionic liquid （HBPIL） vesicle through aqueous self-assembly. By a simple anion-exchange, we achieved the combination of functional sma...This work reports a SO2 derivative-detecting and colorful hyperbranched polymeric ionic liquid （HBPIL） vesicle through aqueous self-assembly. By a simple anion-exchange, we achieved the combination of functional small-molecule probe of acid fuchsin with HBPILs. The obtained HBPIL vesicle displayed ultraviolet absorption at 544 nm, and was used as a novel SO2 derivative sensor with high sensitivity and visualization. Due to the functional ion pairs enriching on the surface, the SO32 detection limit of the HBPILs vesicles was as low as 0.138 gmol/L, which was about 1.5 orders of magnitude lower than that of acid fuchsin.展开更多
以聚乙二醇6000与α-溴代异丁酰溴进行酯化反应得到大分子引发剂PEG6000-Br,使用原子转移自由基聚合(ATRP)法合成了对称三嵌段且聚合度相等的聚甲基丙烯酸二甲胺乙酯-聚乙二醇-聚甲基丙烯酸二甲胺乙酯(PDM_(165)-PEG_(165)-PDM_(165))...以聚乙二醇6000与α-溴代异丁酰溴进行酯化反应得到大分子引发剂PEG6000-Br,使用原子转移自由基聚合(ATRP)法合成了对称三嵌段且聚合度相等的聚甲基丙烯酸二甲胺乙酯-聚乙二醇-聚甲基丙烯酸二甲胺乙酯(PDM_(165)-PEG_(165)-PDM_(165))。利用FTIR和~1HNMR对其结构进行了表征。以p H、电导率测试证明了聚合物溶液的CO_2/N_2循环可逆性,聚合物溶液中通入CO_2后,5 min内,溶液p H值即从7.74下降至5.47,溶液电导率从0.176 m S/cm迅速上升至0.405 m S/cm;继而向溶液中通入N_2,经过30 min后,溶液的p H值和电导率都恢复到初始值。冷冻透射电镜(Cryo-TEM)观察得知,聚合物在水中可自组装形成单层囊泡,通入CO_2后,叔胺被质子化,囊泡解离形成网状结构,导致溶液黏度从3 m Pa·s上升至12 m Pa·s,叔胺质子化由~1HNMR证明,N原子附近的氢位移从δ2.3、2.7、4.1向低场分别移动至δ2.8、3.2、4.3。展开更多
Atom transfer radical polymerization of protected 2 hydroxyethyl acrylate (HEA\|TMS) was conducted to prepare well\|defined bromo\|terminated macroinitiators,which were further allowed to react with large excess amoun...Atom transfer radical polymerization of protected 2 hydroxyethyl acrylate (HEA\|TMS) was conducted to prepare well\|defined bromo\|terminated macroinitiators,which were further allowed to react with large excess amount of C 60 under ATRP condition.A well defined hammer shaped C 60 PHEA was then obtained by hydrolysis of C 60 PHEA TMS under mild conditions.A TEM observation of the association behavior of these well defined hammer like C 60 PHEA macromolecules showed that they assemble into spherical vesicles in water.Their characteristic inner water phase was further confirmed by fluorescence probe method.Also,it was found that the size of vesicles decreased as the increase of molecular weight of PHEA.展开更多
基金financial support from the National Natural Science Foundation of China(21704093)Project funded by China Postdoctoral Science Foundation(2018M632795)+1 种基金Supports Plan for College Science and Technology Innovation Team of Henan Province(16IRTSTHN001)Science&Technology Innovation Talent Plan of Henan Province(174200510018)。
文摘Molecular self-assembly is crucially fundamental to nature.However,the aqueous self-assembly of polymers is still a challenge.To achieve self-assembly of block copolymers [(polyacrylic acid-block-polyethylene glycol-block-polyacrylic acid(PAA68-b-PEG86-b-PAA68)] in an aqueous phase,manganese oxide(MnO2) is first generated to drive phase separation of the PAA block to form the PAA68-b-PEG68-b-PAA68/MnO2 polymeric assembly that exhibits a stable structure in a physiological medium.The polymeric assembly exhibits vesicular morphology with a diameter of approximately 30 nm and high doxorubicin(DOX) loading capacity of approximately 94%.The transformation from MnO2 to Mn2+caused by endogenous glutathione(GSH)facilitates the disassembly of PAA68-b-PEG68-b-PAA68/MnO2 to enable its drug delivery at the tumor sites.The toxicity of DOXloaded PAA68-b-PEG68-b-PAA69/MnO2 to tumor cells has been verified in vitro and in vivo.Notably,drug-loaded polymeric vesicles have been demonstrated,especially in in vivo studies,to overcome the cardiotoxicity of DOX.We expect this work to encourage the potential application of polymer self-assembly.
基金the National Natural Science Foundation of China(Nos.81671806,81571793)CAMS Initiative for Innovative Medicine(Nos.2017-I2M-4-001,2017-I2M-3-020)Fundamental Re search Funds for the Central Universities(Nos.2019PT320028,2019-0831-03)。
文摘Combination therapy such as photothermal therapy(PTT)enhanced chemotherapy is regarded as a promising strategy for cancer treatment.Herein,we developed redox-responsive polymeric vesicles based on the amphiphilic triblock copolymer PCL-ss-PEG-ss-PCL.To avoid the limited therapeutic effect of chemotherapeutic drugs caused by systemic exposures and drug resistance,the redox-sensitive polymeric vesicles were cargoed with two chemotherapeutics:doxorubicin(DOX)and paclitaxel(PTX).Besides,indocyanine green(ICG)was encapsulated,and cell-penetrating peptides and LHRH targeting molecule were modified on the surface of polymeric vesicles.The results indicated that the polymeric vesicles can load different kinds of drugs with high drug loading content,trigger drug release in responsive to the reductive environment,realize high cellular uptake via dual peptides and laser irradiation,and achieve higher cytotoxicity via chemo-photothermal combination therapy.Hence,the redox-responsive LHRH/TAT dual peptides-conjugated PTX/DOX/ICG co-loaded polymeric micelles exhibited great potential in tumor-targeting and chemo-photothermal therapy.
基金financially supported by Scientific Research Innovation Team Project of Provincial Universities in Sichuan Province (No. 13TD0025)
文摘A series of triblock copolymers, containing a CO_2-switchable block poly（2-（dimethylamino）ethyl methacrylate）（PDM） block and two symmetrical hydrophilic blocks polyacrylamide（PAM）, were synthesized using atom transfer radical polymerization（ATRP） method. The p H and conductivity tests showed that the triblock copolymer exhibited switchable responsiveness to CO_2, i.e. a relatively low conductivity of solution could be switched on and off by bubbling and removing of CO_2, and the triblock copolymer aqueous solution displayed a CO_2-switchable viscosity variation. The changes were all attributed to protonation of tertiary amine groups in PDM blocks and proven by 1 H-NMR. Cryogenic transmission electron microscopy and dynamic light scattering characterization demonstrated that the viscosity variation was the result of a unilamellar vesicle-network aggregate structure transition. The release of rhodamine B from the vesicles with and without CO_2 stimuli showed the potential application in drug delivery domains; after CO_2 bubbling, the drug release rate could be accelerated. Finally, reasonable mechanism of CO_2-switchable morphology changes and CO_2-induced drug release was proposed.
基金the financial support of the National Natural Science Foundation of China(Nos.22171255,21774113,and 52021002)。
文摘Comprehensive Summary The size and size distribution of polymeric nanoparticles have great impact on their physicochemical and biological properties.Polymerization-induced self-assembly(PISA)has been demonstrated to be an efficient method to fabricate various polymeric nanoparticles,among which polymeric vesicles have attracted great interest due to their unique hollow structure.
基金This work was supported by the National Natural Science Foundation of China(No.21403292,No.21403293,No.21473249,and No.21673285),and the funding from the Shenzhen city(No.JCYJ20170307150520453).
文摘To understand and control the interfacial properties of polydiacetylenes(PDAs)vesicles withπ-conjugated backbone is very important for their colorimetric sensing of chemical and biological targets.In this work,we adopted 10,12-pentacosadiynoic acid(PCDA)as the model molecule to prepare PDAs vesicles in aqueous solution with different forms(from monomer to blue-to-purple-to-red phase)by controlling the UV irradiation dose.The variations of the interfacial conformation of PDAs vesicles during chromatic transitions were inspected by the adsorption behaviors of probe molecules(4-(4-diethylaminostyry)-1-methylpyridinium iodide,D289)on vesicle surface with surface-specific second harmonic generation(SHG)and zeta potential measurements.Resonant SHG signal from D289 adsorbed on vesicle surface attenuated sharply,and the adsorption free energy as well as the corresponding two-photon fluorescence signal decreased slightly in chromatic transitions.While,the change in the surface density of the adsorbed D289 molecules for PDAs vesicles with different forms was relatively small as estimated from zeta potential measurements.The attenuation of the SHG intensity was thus attributed to the overall order-disorder transition and the changed orientation of D289 molecules caused by the gradual distortion of carboxyl head group driven by backbone perturbation.
基金Project supported by the National Natural Science Foundation of China and Zhong GuanCun Analytical Center.
文摘α-Eleostearic acid and β-eleostearic acid formed vesicles in aqueous medium when an ethanol solution of eleostearic acid was injected rapidly into a vigorously vortexed aqueous phase. Formation of the vesicles was demonstrated by electron microscopic observation and bromothymol blue encapsulation experiments. Polymerizations of the eleostearic acids in the formed vesicles carried out by UV irradiation produced poly-α-eleostearic acid and poly-β-eleostearic acid vesicles.
文摘A cup shape is a dynamic morphology of cells and organelles. With the aim of elucidating the formation of the biotic cup-shaped morphology, this study investigated cup-shaped vesicles consisting of an amphiphilic diblock copolymer from the aspect of synthetic polymer chemistry. Cup-shaped vesicles were obtained by the polymerization-induced self-assembly of poly(methacrylic acid)-block-poly(n-butyl methacrylate-random-methacrylic acid), PMAA-b-P(BMA-r-MAA), in an aqueous methanol solution using the photo nitroxide-mediated controlled/living radical polymerization technique. Field emission scanning electron microscopic observations demonstrated that the cup-shaped vesicles were suddenly formed during the late stage of the polymerization due to the extension of the hydrophobic P(BMA-r-MAA) block chain. During the early stage, the polymerization produced spherical vesicles rather than a cup shape. As the hydrophobic block chain was extended by the polymerization progress, the spherical vesicles reduced the size and were accompanied by the generation of small particles that were attached to the vesicles. The vesicles continued to reduce the size due to further extension of the hydrophobic chain;however, they suddenly grew into cup-shaped vesicles. This growth was accounted for by a change in the critical packing shape of the copolymer due to the hydrophobic chain extension. These findings are helpful for a better understanding of the biotic cup-shaped vesicle formation.
基金supported by the National Basic Research Program(No.2013CB834506)the National Science Fund for Distinguished Young Scholars(No.21225420)+1 种基金the National Natural Science Foundation of China(Nos.91127047,21474062 and 21404070)Program of Shanghai Subject Chief Scientist(No.15XD1502400)
文摘This work reports a SO2 derivative-detecting and colorful hyperbranched polymeric ionic liquid （HBPIL） vesicle through aqueous self-assembly. By a simple anion-exchange, we achieved the combination of functional small-molecule probe of acid fuchsin with HBPILs. The obtained HBPIL vesicle displayed ultraviolet absorption at 544 nm, and was used as a novel SO2 derivative sensor with high sensitivity and visualization. Due to the functional ion pairs enriching on the surface, the SO32 detection limit of the HBPILs vesicles was as low as 0.138 gmol/L, which was about 1.5 orders of magnitude lower than that of acid fuchsin.
文摘以聚乙二醇6000与α-溴代异丁酰溴进行酯化反应得到大分子引发剂PEG6000-Br,使用原子转移自由基聚合(ATRP)法合成了对称三嵌段且聚合度相等的聚甲基丙烯酸二甲胺乙酯-聚乙二醇-聚甲基丙烯酸二甲胺乙酯(PDM_(165)-PEG_(165)-PDM_(165))。利用FTIR和~1HNMR对其结构进行了表征。以p H、电导率测试证明了聚合物溶液的CO_2/N_2循环可逆性,聚合物溶液中通入CO_2后,5 min内,溶液p H值即从7.74下降至5.47,溶液电导率从0.176 m S/cm迅速上升至0.405 m S/cm;继而向溶液中通入N_2,经过30 min后,溶液的p H值和电导率都恢复到初始值。冷冻透射电镜(Cryo-TEM)观察得知,聚合物在水中可自组装形成单层囊泡,通入CO_2后,叔胺被质子化,囊泡解离形成网状结构,导致溶液黏度从3 m Pa·s上升至12 m Pa·s,叔胺质子化由~1HNMR证明,N原子附近的氢位移从δ2.3、2.7、4.1向低场分别移动至δ2.8、3.2、4.3。
文摘Atom transfer radical polymerization of protected 2 hydroxyethyl acrylate (HEA\|TMS) was conducted to prepare well\|defined bromo\|terminated macroinitiators,which were further allowed to react with large excess amount of C 60 under ATRP condition.A well defined hammer shaped C 60 PHEA was then obtained by hydrolysis of C 60 PHEA TMS under mild conditions.A TEM observation of the association behavior of these well defined hammer like C 60 PHEA macromolecules showed that they assemble into spherical vesicles in water.Their characteristic inner water phase was further confirmed by fluorescence probe method.Also,it was found that the size of vesicles decreased as the increase of molecular weight of PHEA.
