Synthesis and self-assembly of stimuli-responsive poly(2-(dimethylamino) ethyl methacrylate)-block-fullerene (PDMAEMA-b-C60) and the demicellization induced by free PDMAEMA chains

Well-defined poly(2-(dimethylamino) ethyl methacrylate)-block-fullerene [60] ((PDMAEMA)-b-C(60)) with a galactose targeting moiety was prepared by atom-transfer radical polymerization (ATRP). This copolymer was designed for possible use as a targeted drug carrier. The chemical composition and the self-assembly behavior were characterized using different techniques, including GPC, NMR, UV, and DLS. The self-assembly of the galactose-functionalized PDMAEMA-b-C(60) structure in aqueous solutions was investigated using dynamic light scattering (DLS) under different pH conditions. At pH 3 and 10, the DLS results showed the presence of both polymeric micelles and unimers. However, a smaller R(h) was observed at pH 10 than at pH 3 because of electrostatic repulsion at low pH values. In addition, free PDMAEMA chains induced the demicellization of self-assembled nanostructures caused by the formation of a charge-transfer complex between PDMAEMA and C(60.) This phenomenon offers possible applications for free-polymer-triggered drug release.     

模仿绿色荧光蛋白的荧光聚合物的合成和光学性质研究

受绿色荧光蛋白(GFP)荧光增强原理启发,采用开环聚合制备了两亲性聚乙二醇-生色团-聚己内酯(PEG-c-PCL)嵌段聚合物.通过核磁共振氢谱和碳谱(1H-,13C-NMR)、傅立叶变换红外光谱(FTIR)、凝胶渗透色谱(GPC)和紫外可见吸收光谱(UV-Vis)等证明其结构和性质.生色团和聚合物有相似的紫外吸收光谱,且最大吸收峰都在371 nm.荧光发射光谱表明,生色团的发射峰在427 nm,但聚合物的荧光发射峰出现了6 nm的红移,这是高分子化引起的结果.透射电镜(TEM)和动态光散射(DLS)证明了该两亲性嵌段聚合物能够组装成为纳米粒子.当聚合物组装成纳米粒子后,荧光强度增大了55倍,并且荧光发射峰出现了14 nm的红移,这些现象可归结于荧光生色团自由旋转的限制和组装导致的相互作用增强.     

Triple stimuli-responsive polymers based on pyrene-functionalized poly(dimethylaminoethyl methacrylate): synthesis,self-assembled nanoparticles and controlled release

A series of photo, temperature, and pH-responsive polymers have been synthesized by the quaternization of poly(dimethylaminoethyl methacrylate) (PDMAEMA) with 1-(bromomethyl)pyrene. Nanoparticles self-assembled from the pyrene-functionalized polymers in aqueous solution are demonstrated by transmission electron microscopy (TEM) and dynamic light scattering (DLS), the morphology of which can be changed under external stimulation by UV light, temperature, and pH. With the increase of the functionalization degree, the lower critical solution temperature (LCST) and the photo response of the pyrene-functionalized polymer increases, while the critical aggregation concentration (CAC) and the pH response decreases. The controlled release of encapsulated molecules such as Nile Red (NR)and anticancer drug doxorubicin (DOX) can be achieved under the triple stimulation from the self-assembled nanoparticles.     

非共价键自组装制备聚对苯撑乙炔/聚丙烯酸水溶性荧光纳米粒子及其光物理行为研究

通过功能化聚对苯撑乙炔(含羟基与氨基)和聚丙烯酸之间的非共价键自组装制备了一系列含共轭聚合物的水溶性荧光纳米粒子, 并进行了相关结构和光学性质表征. 研究表明, 纳米粒子的大小和聚丙烯酸/聚对苯撑乙炔质量比直接相关. 光物理性质研究表明, 形成水溶性纳米粒子后, 疏水的聚苯撑乙炔链在纳米粒子中易于形成π-链间聚集, 其光物理性质与其在薄膜态时相似.     

聚乙二醇-b-聚(D,L-丙交酯-co-碳酸丙二酯)的胶束化及其药物控释研究

通过开环共聚合成了由D,L-丙交酯、碳酸丙二酯和聚乙二醇构成的两亲性嵌段共聚物(PETLA),研究了PETLA胶束化及药物控释行为.嵌段共聚物和胶束通过核磁共振(1H-NMR)、荧光分光光度计、凝胶渗透色谱(GPC)、动态光散射(DLS)、透射电镜(TEM)和紫外光谱(UV)表征.实验结果发现临界胶束浓度随共聚物疏水链段长度增加而减小,胶束直径随疏水链段长度增加而增大.透射电镜照片表明载药胶束MT1直径为30~40nm,呈规则球形.体外释药表明9-NC以可控方式释放,突释后药物释放速率接近零级恒速.     

Star-PDMAEMA-β-CD-Stabilized Colloidal Gold Nanoparticles: Synthesis,Characterization and pH-Controlled Assembly

Colloidal gold nanoparticles were prepared through in situ reduction in the presence of water-soluble star homopolymer with β-cyclodextrin core and poly[2-(dimethylamino) ethyl methacrylate] arms (star PDMAEMA-β-CD) at ambient temperature. In this process, star PDMAEMA-β-CD acted as both reducing agent and stabilizing agent for gold nanoparticles. More importantly, the optical properties and the morphology of star-PDMAEMA-β-CD-stabilized colloidal gold nanoparticles were sensitive to the solution pH due to structural changes of the polymer. Different assemblies can be formed by tuning the pH of the medium. Fourier transform infrared (FT-IR), UV-Vis absorption spectroscopy, transmission electron microscopy (TEM), dynamic laser light scattering (DLS) and X-ray diffraction (XRD) were used to characterize the synthetic gold nanoparticles and the pH-controlled assembly of gold nanoparticles.     

Synthesis and Self-Assembly Behaviors of Four-Arm Star Block Copolymers Poly(ϵ-caprolactone)-b-poly(2- (diethylamino) ethyl methacrylate)) in Aqueous Solution

Four-arm star block polymers consisting of hydrophobic poly(?-caprolactone) (PCL) block and hydrophilic poly(2-(diethylamino) ethyl methacrylate)) (PDEAEMA) block were successfully synthesized by ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP). Chain lengths of PDEAEMA segments were varied to obtain a series of star copolymers with different hydrophilic/hydrophobic ratio, which were desired for self-assembly study. Dynamic light scattering (DLS) and transmission electron microscopic (TEM) were used to study their self-assembly behavior. In the PBS solution with different pH value, the star polymers formed micelles or nanoparticles. Furthermore, the morphologies of the micelles were also pH-dependent. Critical micelle concentrations of star copolymers changed from 5.0 to 17.5 mg/L with the increase of hydrophilic block length or the pH decrease. Moreover, a steady increase was found on the micelles diameters when the pH decreased from 7.0 to 3.0. The low CMC value and slight changes on micelle diameter indicated that the micelle remained stable under the changing external stimulus.     

Self-assembly and emulsification of poly{[styrene-alt-maleic acid]-co-[styrene-alt-(N-3,4-dihydroxyphenylethyl-maleamic acid)]}

Self-assembled polymeric micelles can be used as efficient particulate emulsifiers. To explore the relationship between the structure and the oil-water interfacial behavior of the micelle emulsifiers, a new type of amphiphilic random copolymer, poly{(styrene-alt-maleic acid)-co-[styrene-alt-(N-3,4-dihydroxyphenylethyl-maleamic acid)]} (SMA-Dopa), was synthesized, self-assembled into micelles, and used as emulsifiers. SMA-Dopa was synthesized via an aminolysis reaction between dopamine and commercial alternating copolymer poly(styrene-alt-maleic anhydride) (SMA). Dopamine moiety facilitated the self-assembly of the SMA-Dopa in selective-solvent into stable micelles, and increased the adsorption of the SMA-Dopa at the oil-water interface. Additionally, the structural transition of the self-assembled SMA-Dopa52 micelles in response to pH and salinity changes were confirmed by means of TEM, AFM, DLS, aqueous electrophoresis techniques, potentiometric titration, and pyrene fluorescence probe methods. Micelles shrunk with increasing salinity, and flocculation of the shrunken primary micelles occurred at salt concentration exceeding 0.1 M. The micelles swelled with increasing pH, and the disassociation of the SMA-Dopa52 micelles occurred at pH above approximately 6.5. The structure of the micelles plays a crucial role in the oil-water interfacial performance. Micelles with various structures were used as emulsifiers to adsorb at the styrene-water and toluene-water interfaces. The emulsifying characteristics demonstrated that self-assembled SMA-Dopa52 micelles with moderately swollen structure (at 2 < pH < 6) combine the advantages of the solid particulate emulsifiers and polymeric surfactants, possessing excellent emulsifying efficiency and good emulsion stability. Moreover, the emulsifying performance of the SMA-Dopa52 micelles could be enhanced by the addition of salt.     

端基结构对超支化聚合物静电吸附自组装行为的影响

研究了3种具有相同骨架结构、不同端基的超支化聚合物与线型聚阳离子(PDAC)的静电吸附自组装.结果表明,超支化聚合物的组装过程与线型弱酸聚合物相似,都受溶液pH值与无机盐浓度的影响,但影响程度随端基结构不同而变化.此外,对以超支化聚合物为最外层的不同自组装膜的表面形貌及接触角进行了表征,其表面形貌及亲水性随端基结构的不同而不同.     

Synthesis and Characterization of Poly[bis(p-oxybenzaldehyde diethylamino)phosphazenes], Poly[bis(p-oxybenzaldehyde)phosphazenes], Poly[bis(diethylamino)phosphazenes] and their Self- assembly Behaviors

Polydichlorophosphazenes (PDCP) were synthesized through ring opening polymerization of hexachlorocyclotriphosphazene (HCCP). The polymerization behavior of HCCP under varying conditions of time and amount of catalyst was investigated. The chlorine atoms in polydichlorophosphazenes (PDCP) were substituted with p-oxybenzaldehyde and (or) diethylamine to synthesize poly[bis(p-oxybenzaldehyde diethylamino)phosphazenes](PPOBADEAP), poly[bis(p-oxybenzaldehyde)phosphazenes] (PPOBAP) and poly[bis(diethyl amino) phosphazenes] (PDEAP). The supporting evidence for the success of this synthesis was provided by nuclear magnetic resonance (¹H-NMR, and ³¹P-NMR), gel permeation chromatography (GPC), and energy-dispersive X-ray spectroscopy (EDAX). The self-assembly behavior of PPOBADEAP, PPOBAP and PDEAP was observed in different solvents by the same concentration of polymers. The optical microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images indicated that PPOBADEAP formed various morphologies in different solvents while PPOBAP and PDEAP did not show self-assembly behavior at the same conditions.     

Reversible aggregation of gold nanoparticles induced by pH dependent conformational transitions of a self-assembled polypeptide

Controlling the stable structures of metallic nanoparticles on mesoscopic and macroscopic length scales is of great interest in nanotechnology. Here, this task is accomplished using a synthetic biopolymer that is responsive to external stimuli and undergoes changes in secondary structure. Reversible aggregation of gold nanoparticles (GNP) is induced by pH dependent changes in a self-assembled monolayer of disulfide modified poly(L-glutamic acid) (SSPLGA) with M(w) approximately 27000. The disulfide anchoring group drives chemisorption onto the gold nanoparticles and leads to the formation of a self-assembled monolayer. Characterization of the modified GNP and its aggregation behavior is performed using dynamic light scattering (DLS), UV-vis and IR spectroscopy, and transmission electron microscopy (TEM). Experimental results show that decrease in pH near 5.5 leads to aggregation of the modified GNP. The change in aggregation behavior with pH occurs within minutes, is reversible, and happens within a narrow range of pH from about 4.5 to 5.5. Comparison with literature data on molar enthalpy of hydrogen bonding, specific optical rotation, and ionization for the helix-coil transition of PLGA indicates that the aggregation of the SSPLGA modified GNP corresponds to the transition in the secondary structure of the polyacid.     

以磁纳米粒为核的pH敏感型聚谷氨酸树状分子药物载体

报道了一种新的肽类树枝状分子改性磁性纳米药物载体.以天然氨基酸L-谷氨酸为原料,通过收敛法合成了聚(L-谷氨酸)树状分子,将多巴胺配体键合到聚(L-谷氨酸)树状分子上,用核磁(1H-NMR)、质谱(MS)对合成出的树状分子配体进行了表征,然后通过配体交换对四氧化三铁磁纳米粒表面进行多功能化.以阿霉素为模型药物通过pH敏...     

ARGET ATRP 与ROP 结合制备pH 响应两亲性聚合物分子刷及其自组装研究

结合电子转移活化剂再生-原子转移自由基聚合(ARGET ATRP)和开环聚合(ROP)法合成了一种具有无规疏水/ pH 响应结构的两亲性聚合物分子刷聚(甲基丙烯酸聚丙交酯酯-co-甲基丙烯酸)-b-聚甲基丙烯酸单甲氧基聚乙二醇酯 [P(PLAMA-co-MAA)-b-PPEGMA]. 通过核磁共振氢谱(¹H NMR)和凝胶渗透色谱(GPC)表征了聚合物的结构、分子量及分子量分布. 优化了反应条件并合成出分子量可控、分子量分布窄的聚合产物. 采用动态光散射法(DLS)、扫描电子显微镜(SEM)研究了聚合物分子刷在水溶液中自组装胶束的粒径、形貌及pH 响应行为. P(PLAMA-co-MAA)-b-PPEGMA 自组装形成粒径分布均匀的球形胶束. 且随着溶液pH 值从7 降低至3, 胶束中的PMAA 逐渐去离子化, 溶胀的胶束逐渐收缩, 粒径由200～300 nm 减小至150 nm 左右; 但当pH 值减小到2 以下, 胶束表面电荷量非常小, 胶束聚集, 使得粒径增大.     

Self-assembly of poly(ferrocenyldimethylsilane)-poly(benzyl ether) linear-dendritic organometallic polymer

A kind of linear-dendritic organometallic polymer poly(ferrocenyldimethylsilane)-poly(benzyl ether) (PFS-PBE) was synthesized and the self-assembly behaviors of the polymer was studied, which has illuminated the formation of multiple morphologies and, in particular, adjusting the concentration of polymers and adding poly(benzyl ether) into self-assembled solution can form different size and morphology. Furthermore, it was found that the aging time of samples could affect self-assembled morphology. The micelle formation mechanisms were also demonstrated.     

Hydrogen-bonding-driven self-assembly of PEGylated organosilica nanoparticles with poly(acrylic acid) in aqueous solutions and in layer-by-layer deposition at solid surfaces

PEGylated organosilica nanoparticles have been synthesized through self-condensation of (3-mercaptopropyl)trimethoxysilane in dimethyl sulfoxide into thiolated nanoparticles with their subsequent reaction with methoxypoly(ethylene glycol) maleimide. The PEGylated nanoparticles showed excellent colloidal stability over a wide range of pH in contrast to the parent thiolated nanoparticles, which have a tendency to aggregate irreversibly under acidic conditions (pH < 3.0). Due to the presence of a poly(ethylene glycol)-based corona, the PEGylated nanoparticles are capable of forming hydrogen-bonded interpolymer complexes with poly(acrylic acid) in aqueous solutions under acidic conditions, resulting in larger aggregates. The use of hydrogen-bonding interactions allows more efficient attachment of the nanoparticles to surfaces. The alternating deposition of PEGylated nanoparticles and poly(acrylic acid) on silicon wafer surfaces in a layer-by-layer fashion leads to multilayered coatings. The self-assembly of PEGylated nanoparticles with poly(acrylic acid) in aqueous solutions and at solid surfaces was compared to the behavior of linear poly(ethylene glycol). The nanoparticle system creates thicker layers than the poly(ethylene glycol), and a thicker layer is obtained on a poly(acrylic acid) surface than on a silica surface, because of the effects of hydrogen bonding. Some implications of these hydrogen-bonding-driven interactions between PEGylated nanoparticles and poly(acrylic acid) for pharmaceutical formulations are discussed.     

Synthesis and supramolecular organization of amphiphilic diblock copolymers combining poly(N,N-dimethylamino-2-ethyl methacrylate) and poly(epsilon-caprolactone)

Well-defined poly(epsilon-caprolactone) (PCL)/poly(N,N-dimethylamino-2-ethyl methacrylate (PDMAEMA) diblock copolymers were synthesized, and their self-assembly was investigated as micelles both in aqueous solutions and in thin solid deposits. The synthetic approach combines controlled ring opening polymerization (ROP) of epsilon-caprolactone (CL) and atom transfer radical polymerization (ATRP) of N,N-dimethylamino-2-ethyl methacrylate (DMAEMA). Diblock copolymers were prepared by ROP of CL initiated by (Al(OiPr)3), followed by quantitative reaction of the PCL hydroxy end-groups with bromoisobutyryl bromide. The alpha-isopropyloxy omega-2-bromoisobutyrate poly(epsilon-caprolactone) (PCL-Br) obtained was used as a macroinitiator for the ATRP of DMAEMA. The molecular characterization of those diblock copolymers was performed by 1H NMR spectroscopy and gel permeation chromatography (GPC) analysis. The self-assembly of the copolymers into micellar aggregates in aqueous media was followed with dynamic light scattering (DLS), as a function of concentration and the pH. In parallel, the morphology of the solid deposits of those micelles was examined with atomic force microscopy (AFM).     

双亲支链梳形共聚物的合成及其自乳化负载药物性能

通过可逆加成-断裂链转移(RAFT)聚合制备出聚甲基丙烯酸缩水甘油酯(PGMA),经过叠氮钠与PGMA环氧基团的反应引入叠氮基和羟基,然后依次通过端炔基聚乙二醇(PEG-alk)与叠氮基的点击反应,己内酯(CL)在羟基存在下的开环聚合反应,获得双亲支链梳形共聚物(PGMA-g-PEG/PCL)。利用该梳形共聚物的两亲性,在氯仿-水混合体系中,进行自乳化高效负载阿霉素(DOX),得到负载DOX的纳米粒子。利用核磁共振氢谱、红外光谱和凝胶渗透色谱确认了最终产物及其前体聚合物的结构。利用动态光散射、紫外可见分光光度计和扫描电镜研究该载药粒子在pH为7.0和5.0的水溶液中的释放。结果表明:该纳米粒子平均粒径约为100nm,该粒子能有效释放DOX,在酸性条件下释放速率加快,且伴随PCL的降解。     

Morphological transition of nanostructures of self-assembled block copolymers by stimuli-induced conformational changes in the hydrophilic block

The morphological control of nanostructures created by the self-assembly of macromolecular building blocks in solution has practical importance because the structural parameters of nanostructures greatly affect their physical and chemical behavior in solution, for example, pharmacokinetics. Herein, we report that the stimuli-induced changes to the conformation of the hydrophilic polymer block of a block copolymer (BCP), in this case branched-linear poly(ethylene glycol)-b-poly(styrene) BCPs, are translated to changes in the morphology of the BCP self-assemblies in solution. Specifically, the cone angle between the poly(ethylene glycol) arms in the tri-arm hydrophilic block equipped with pyridyl units in the scaffold can be changed by varying the self-assembly conditions, thus affecting the packing parameter (p) of the BCP. Upon increasing the cone angle by protonating the pyridyl units, the self-assembled BCP structures underwent changes consistent with a reduction in the p value. In contrast, the chelation of zinc metal cations (Zn²⁺) to the pyridyl groups resulted in the conformation of the hydrophilic block taking on a closed form, resulting in an apparent increase in the p value of the BCP. Our results could be applied to stimuli-dependent morphological transitions of other self-assembled BCP nanostructures in solution.     

银纳米粒子的一步合成与表征

在水和乙醇溶液中,以对巯基苯胺作为还原剂,利用一步法合成了银纳米微粒,并利用拉曼光谱仪考察了对巯基苯胺在银纳米微粒表面的自组装行为.结果表明,合成的银纳米微粒的形貌与介质的pH值密切相关;对巯基苯胺可在银纳米微粒表面自组装.     

Poly(acrylamide-co-2-acrylamido-2-methyl-1-propanesulfonic Acid) Nanogels made by Inverse Microemulsion Polymerization

Poly(acrylamide-co-2-acrylamido-2-methyl-1-propanesulfonic acid) poly(AM-co-AMPSA) nanogels were prepared through inverse microemulsion polymerization with low AMPSA/AM weight ratio in the feed (up to 0.3357) to control particle size and pH sensitivity. An aqueous solution of AM and AMPSA was used as the dispersed phase for microemulsion with sodium bis(2-ethylhexyl) sulfosuccinate (AOT)/Toluene solution as the dispersion medium. The polymerization was carried out at 50°C in the presence of 2,2-azobisisobutyronitrile (AIBN) and N,N′-methylenebisacrylamide (NMBA) as an initiator and a crosslinker, respectively. Fourier transform infra red spectrophotometer (FTIR) and ¹H-nuclear magnetic resonance spectroscopy (¹H-NMR) studies confirm the occurrence of copolymerization between the two monomers. The hydrodynamic diameter of synthesized poly(AM-co-AMPSA) nanogels is found to be in the range of 63–125nm as measured by dynamic light scattering (DLS). The equilibrium swelling and the effect of pH on particle size of copolymer nanogel are found to depend on the copolymer composition. The polymer chain composition, thermal properties and morphology of nanogels were measured by elemental analysis, thermogravimetric analyzer (TGA) and differential scanning calorimeter (DSC), and scanning electron microscope (SEM), respectively.