两亲型聚L-亮氨酸-聚乙二醇单甲醚嵌段共聚物的合成与表征

开环聚合;生物降解共聚物;两亲型聚L-亮氨酸-聚乙二醇单甲醚嵌段共聚物的合成与表征     

Biocompatible polymer vesicles from biamphiphilic triblock copolymers and their interaction with bovine serum albumin

The self-assembly of the biamphiphilic triblock copolymer poly(ethylene oxide)-b-poly(caprolactone)-b-poly(acrylic acid) into polymer vesicles is studied. The vesicles provide both biocompatibility and biodegradability. Moreover, the biamphiphilic nature of the triblock copolymer provides different surface properties in the interior and in the outer interface of the vesicles. Preparation of the aggregates by direct dissolution of the copolymer in a solution of albumin does not alter the morphology of the aggregates, and thus, they have the potential to immobilize protein molecules. Since a part of the protein is encapsulated in the interior of the vesicles, they can be used as nanocontainers. A further fraction of the protein is bound to the outer interface, which is primarily composed of the poly(acrylic acid) tails. Immobilization of protein on the outer interface can stabilize the colloidal particles and also provide them with a biofunctional component.     

Thermoreversible gelation of poly(ethylene oxide) biodegradable polyester block copolymers. II

Poly(ethylene oxide)-b-poly(L-lactic acid) (PEO-PLLA) diblock copolymers were synthesized via a ring opening polymerization from poly(ethylene oxide) and l -lactide. Stannous octoate was used as a catalyst in a solution polymerization with toluene as the solvent. Their physicochemical properties were investigated by using infrared spectroscopy, ¹H-NMR spectroscopy, gel permeation chromatography, and differential scanning calorimetry, as well as the observational data of gel-sol transitions in aqueous solutions. Aqueous solutions of PEO-PLLA diblock copolymers changed from a gel phase to a sol phase with increasing temperature when their polymer concentrations are above a critical gel concentration. As the PLLA block length increased, the gel-sol transition temperature increased. For comparison, diblock copolymers of poly(ethylene oxide)-b-poly(l -lactic acid-co-glycolic acid) [PEO-P(LLA/GA)] and poly(ethylene oxide)-b-poly(dl -lactic acid-co-glycolic acid) [PEO-P(DLLA/GA)] were synthesized by the same methods, and their gel-sol transition behaviors were also investigated. The gel-sol transition properties of these diblock copolymers are influenced by the hydrophilic/hydrophobic balance of the copolymer, block length, hydrophobicity, and stereoregularity of the hydrophobic block of the copolymer. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 2207–2218, 1999     

聚(γ-苄基-L-谷氨酸)-b-聚(γ-十二烷基-L-谷氨酸)二嵌段共聚物的合成与表征

合成一种分子量分布窄、两嵌段侧链不同的新型聚(γ-苄基-L-谷氨酸)和聚(γ-十二烷基-L-谷氨酸)的二嵌段聚肽(poly(γ-benzyl-L-glutamate)-b-poly(γ-dodecyl-L-glutamate),PBLG-b-PDLG),并研究该嵌段聚肽的分子结构、热性能及液晶性.PBLG-b-PDLG的合成是利用N-羧酸内酸酐(N-carbonyl anhydride,NCA)法,以正己胺为引发剂,在0℃的条件下的氯仿溶液中,先将γ-苄基-L-谷氨酸NCA开环聚合获得了末端带胺基的活性PBLG-NH2沉淀后,再以其为引发剂加入γ-十二烷基-L-谷氨酸的NCA继续反应.氢核磁共振波谱(1H-NMR)和凝胶渗透色谱(GPC)用于表征两嵌段的摩尔比、分子量及其分布,发现嵌段聚肽的分子量分布只有1.07～1.09.由红外光谱(IR)的分析得知PBLG-b-PDLG的二次结构为刚直棒状的α-螺旋结构.利用示差扫描量热分析法(DSC)考察材料的热性质,发现不同组成的PBLG-b-PDLG有不同的热行为,而在100℃附近都出现了微弱的热致相转变.采用偏光显微镜观察PBLG-b-PDLG磁场取向膜的相变行为中发现其相结构不同于一般无规共聚物所呈现的胆甾液晶结构,同时用在PBLG-b-PDLG的二氯乙烷溶致液晶溶液中观察到一般近晶相所呈现的扇形织构.     

酶触发聚合物囊泡-核交联胶束转变用于响应性抗菌剂释放

通过使用药物运载体系来提高抗菌物质的使用效率是应对抗生素耐药性的有效途径.本文报道了一种制备细菌酶响应聚合物囊泡作为"智能型"抗菌剂载体的方法.通过可逆加成-断裂链转移聚合(RAFT)制备的脂酶和硝基还原酶响应的二嵌段共聚物PEG-b-PA和PEG-b-PN,能够在水溶液中自组装形成聚合物囊泡组装体.该囊泡组装体在没有酶存在的条件下相对稳定,而在脂酶或硝基还原酶的作用下发生从囊泡到核交联胶束的形貌转变.基于这一转变过程实现了负载在囊泡中的抗菌剂(三氯生,抗菌肽Parasin Ⅰ和溶菌酶)的选择性释放,并研究了针对大肠杆菌(E.coli,革兰氏阴性菌)、金黄色葡萄球菌(S.aureus,革兰氏阳性菌)和白色念珠菌(C.albicans,真菌)的生长抑制效果.     

Methionine sulfoxide and phosphonate containing double hydrophilic block copolypeptides and their mineralization of calcium carbonate

In effort to address challenges in the efficient synthesis of highly functional block copolypeptides, we report use of a combination of functional monomer polymerization and postpolymerization modification to obtain new double hydrophilic block copolypeptides with desirable properties. We prepared copolymers that contain discrete hydrophilic, nonionic poly(l‐ methionine sulfoxide) and Ca²⁺ ion binding poly(l ‐phosphonohomoalanine) segments. The facile and selective postpolymerization conversion of inexpensive, readily prepared poly(l ‐methionine) segments into nonionic, hydrophilic poly(l ‐methionine sulfoxide) segments reduces the need for use of combinations of protecting groups. The complex copolypeptides prepared using this strategy were able to promote formation of CaCO₃ microspheres with tunable polymorphism. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3707–3712     

Adsorption of poly(ethylene oxide)-b-poly(epsilon-caprolactone) copolymers at the silica-water interface

The adsorption of amphiphilic poly(ethylene oxide)-b-poly(epsilon-caprolactone) and poly(ethylene oxide)-b-poly(gamma-methyl-epsilon-caprolactone) copolymers in aqueous solution on silica and glass surfaces has been investigated by flow microcalorimetry, small-angle neutron scattering (SANS), surface forces, and complementary techniques. The studied copolymers consist of a poly(ethylene oxide) (PEO) block of M(n) = 5000 and a hydrophobic polyester block of poly(epsilon-caprolactone) (PCL) or poly(gamma-methyl-epsilon-caprolactone) (PMCL) of M(n) in the 950-2200 range. Compared to homoPEO, the adsorption of the copolymers is significantly increased by the connection of PEO to an aliphatic polyester block. According to calorimetric experiments, the copolymers interact with the surface mainly through the hydrophilic block. At low surface coverage, the PEO block interacts with the surface such that both PEO and PCL chains are exposed to the aqueous solution. At high surface coverage, a dense copolymer layer is observed with the PEO blocks oriented toward the solution. The structure of the copolymer layer has been analyzed by neutron scattering using the contrast matching technique and by tapping mode atomic force microscopy. The experimental observations agree with the coadsorption of micelles and free copolymer chains at the interface.     

Reversible inside-out micellization of pH-responsive and water-soluble vesicles based on polypeptide diblock copolymers

The synthesis of a new zwitterionic diblock copolymer poly(l-glutamic acid)-b-poly(l-lysine) (PGA-b-PLys) is described, and its self-assembly into schizophrenic vesicles that can reversibly be produced in moderate acidic or basic aqueous solutions is reported. These pH-sensitive nanoparticles are expected to be very promising candidates in macromolecular nanobiotechnologies.     

聚(L-丙氨酸)-聚羟乙基谷氨酰胺双嵌段两亲性共聚多肽的合成及其在水溶液中的自组装

利用光气法分别以L-谷氨酸和L-丙氨酸为原料,合成了γ-谷氨酸苄酯-NCA单体和L-丙氨酸-NCA单体,再以三乙胺为引发剂,合成了聚(L-丙氨酸)-聚(γ-谷氨酸苄酯)(PLA50-b-PBLG20)双嵌段共聚多肽,并用乙醇胺对其中的PBLG嵌段进行亲核取代,把疏水性的苄酯侧链变为亲水性的羟烷酰胺侧链,得到双亲性的聚(L-丙氨酸)-聚羟乙基谷氨酰胺(PLA-b-PHEGA)双嵌段共聚多肽.利用红外光谱和核磁共振谱对产物进行了表征,用TEM研究了双嵌段共聚多肽PLA50-b-PHEGA20在水溶液中的自组装.研究结果表明,双嵌段共聚多肽在水溶液中可自组装形成囊泡.     

Preparation and characterization of polyion complex micelles with a novel thermosensitive poly(2-isopropyl-2-oxazoline) shell via the complexation of oppositely charged block ionomers

Novel thermosensitive polyion complex (PIC) micelles were prepared in an aqueous medium based on the complexation of a pair of oppositely charged block ionomers, poly(2-isopropyl-2-oxazoline)-b-poly(amino acid)s (PiPrOx-b-PAA), containing thermosensitive PiPrOx segments. The controlled synthesis of PiPrOx-b-PAA was achieved via the ring-opening anionic polymerization of N-carboxyanhydrides (NCA) of either eta-benzyloxycarbonyl-l-lysine (Lys(Z)-NCA) or beta-benzyl-l-aspartate (BLA-NCA) with omega-amino-functionalized PiPrOx macroinitiators and the subsequent deprotection reaction under acidic or basic conditions. Gel permeation chromatography (GPC) and 1H NMR spectroscopy revealed that the syntheses of two block ionomers, poly(2-isopropyl-2-oxazoline)-b-poly(l-lysine) [PiPrOx-P(Lys)] and poly(2-isopropyl-2-oxazoline)-b-poly(aspartic acid) [PiPrOx-P(Asp)], proceeded almost quantitatively to give samples with a narrow molecular weight distribution (Mw/Mn 相似文献   

聚丙烯酸-b-聚(N-异丙基丙烯酰胺)嵌段共聚物的合成及其温度和pH值敏感性自组装研究

通过原子转移自由基聚合方法, 在丁酮/异丙醇混合溶剂中合成了分子量可控和分布较窄的聚丙烯酸叔丁酯-b-聚N-异丙基丙烯酰胺(PtBA-b-PNIPAM)嵌段共聚物, 用GPC和 1 H NMR对其结构进行了表征. PtBA-b-PNIPAM在甲苯中水解得到聚丙烯酸-b-聚N-异丙基丙烯酰胺(PAA-b-PNIPAM). 用动态光散射技术对PAA-b-PNIPAM在水溶液中的自组装行为随pH值和温度变化的响应进行了初步研究.     

Hierarchical self-assembly in diblock copolypeptides of poly(γ-benzyl-l-glutamate) with poly poly(l-leucine) and poly(O-benzyl-l-tyrosine)

Block copolypeptides with their inherent nanometer length scale of phase separation, provide means of manipulating the type (α-helices, β-strands) and persistence of peptide secondary structures. Two such examples are employed based on the α-helical poly(γ-benzyl-l-glutamate) (PBLG) polypeptide as one block and poly(l-leucine) (α-helical) or poly(O-benzyl-l-tyrosine) (POBT) (β-strands) as the second block. Although both secondary structures are present in the copolypeptides the effect of nano-scale confinement is to induce folding in the POBT β-sheets and to maintain the defected α-helices of PBLG and PLEU with a limited lateral coherence.     

Self-assembly behavior of pH- and thermosensitive amphiphilic triblock copolymers in solution: experimental studies and self-consistent field theory simulations

We investigated, both experimentally and theoretically, the self-assembly behaviors of pH- and thermosensitive poly(L-glutamic acid)- b-poly(propylene oxide)-b-poly(L-glutamic acid) (PLGA-b-PPO-b-PLGA) triblock copolymers in aqueous solution by means of transmission electron microscopy (TEM), scanning electron microscopy (SEM), dynamic light scattering (DLS), circular dichroism (CD), and self-consistent field theory (SCFT) simulations. Vesicles were observed when the hydrophilic PLGA block length is shorter or the pH value of solution is lower. The vesicles were found to transform to spherical micelles when the PLGA block length increases or its conformation changes from helix to coil with increasing the pH value. In addition, increasing temperature gives rise to a decrease in the size of aggregates, which is related to the dehydration of the PPO segments at higher temperatures. The SCFT simulation results show that the vesicles transform to the spherical micelles with increasing the fraction or statistical length of A block in model ABA triblock copolymer, which corresponds to the increase in the PLGA length or its conformation change from helix to coil in experiments, respectively. The SCFT calculations also provide chain distribution information in the aggregates. On the basis of both experimental and SCFT results, the mechanism of the structure change of the PLGA- b-PPO- b-PLGA aggregates was proposed.     

Morphological change of the micelle of poly(styrene)-b-poly(2-vinylpyridine)-b-poly(ethylene oxide) induced by binding of sodium dodecyl sulfate

Morphological change of a micelle of poly(styrene)-b-poly(2-vinylpyridine)-b-poly(ethylene oxide) (PS-PVP-PEO) polymer was induced by binding sodium dodecyl sulfate (SDS) to the PVP block in acidic aqueous solutions. The change in the size of SDS/PS-PVP-PEO complexes was detected by dynamic light scattering measurements and atomic force microscopy, and the binding of SDS was confirmed by zeta-potential measurements. When the micelle was free from SDS in acidic aqueous solutions, the hydrodynamic diameter of the micelle was 216 nm, reflecting the extended conformation of the PVP block due to the repulsion between protonated pyridine units. As the cationic PVP block was electrically neutralized with anionic SDS, the diameter was gradually reduced concomitant with the decrease in zeta-potential and finally reached 175 nm when the PVP block was completely neutralized. The decrease in the diameter shows the morphological change of the PVP block from extended to shrunken forms. Further addition of SDS did not cause the changes of the diameter nor zeta-potential. This indicates that SDS was not bound to the PS-PVP-PEO polymer after the PVP block was fully neutralized and that the hydrophobic binding of SDS to the polymer was negligible due to the low concentration of SDS.     

聚乳酸-b-聚(N~ε-苄氧羰基-L-赖氨酸)-b-聚乙二醇的合成与表征

用端氨基聚乳酸做引发剂,在DMF中引发Nε-苄氧羰基-L-赖氨酸酐(Lys(Z)-NCA)聚合,合成了端氨基聚(Nε-苄氧羰基-L-赖氨酸)-b-聚乳酸两嵌段共聚物.以端羧基聚乙二醇经NHS活化与端氨基聚(Nε-苄氧羰基-L-赖氨酸)-b-聚乳酸偶联,合成了聚(乳酸-b-Nε-苄氧羰基-L-赖氨酸-b-乙二醇)三嵌段聚合物.利用IR、1H-NMR、GPC和TEM对它们的结构、形态进行了表征,结果表明,所合成的分子量可控、分子量分布窄(Mw/Mn=1.07)的嵌段共聚物,酰化反应产率达70%以上.同时聚乙二醇和Nε-苄氧羰基-L-赖氨酸被引入到聚乳酸主链中,在聚合物侧链脱保护后有望改善聚乳酸的细胞亲和性。     

Self-assembly of charged amphiphilic diblock copolymers with insoluble blocks of decreasing hydrophobicity: from kinetically frozen colloids to macrosurfactants

We have investigated the self-assembly properties in aqueous solution of amphiphilic diblock copolymers with insoluble blocks of different hydrophobicity and demonstrated that the condition to obtain dynamic micelles is to design samples with insoluble blocks of low enough hydrophobicity. We focus here on results with new water-soluble amphiphilic diblock copolymers poly(diethyleneglycol ethylether acrylate)-b-poly(acrylic acid), or PDEGA-b-PAA. The physical characteristics of PDEGA-b-PAA micelles at high ionization have been determined by small angle neutron scattering (SANS). We show that PDEGA-b-PAA samples form micelles at thermodynamic equilibrium. The critical micelle concentrations (CMCs) decrease strongly with ionic strength and temperature due to a solvent quality decrease for, respectively, the corona and the core. This behavior of reversible aggregation is remarkable as compared to the behavior of kinetically frozen aggregation that has been widely observed with samples of similar architecture and different hydrophobic blocks, for example, poly(styrene)-b-poly(acrylic acid), PS-b-PAA, and poly(butyl acrylate)-b-poly(acrylic acid), PBA-b-PAA. We have measured the interfacial tension between water and the homopolymers PDEGA and PBA at, respectively, 3 and 20 mN/m at room temperature, which permits one to estimate the energy cost to extract a unimer from a micelle. The results are consistent with a micelle association that is fast for PDEGA-b-PAA and kinetically frozen PBA-b-PAA. Hence, PDEGA-b-PAA samples form a new system of synthetic charged macrosurfactant with unique properties of fast dynamic association, tunable charge, and water solubility even at temperatures and NaCl concentrations as high as 65 °C and 1 M.     

Three-dimensionally packed nanohelical phase in chiral block copolymers

Chirality-driven microphase-separated morphology, poly(l-lactide) (PLLA) left-handed nanohelices hexagonally packed in PS matrix, was obtained from chiral diblock copolymers, poly(styrene)-b-poly(l-lactide). This is perhaps for the first time; the helical superstructures of chiral block copolymers were generated in the bulk and self-assembled to a two-dimensionally (2D) packed lattice. Now, the analyses of block copolymer thermodynamics should be complicated by the chiral entities of constituted components. Orderly packed nanohelical channels can be obtained after hydrolysis, and this provides new opportunities for block copolymer applications in the fields of nanosciences.     

Novel thermoresponsive and pH-responsive aggregates from self-assembly of triblock copolymer PSMA-b-PNIPAAm-b-PSMA

A series of novel triblock copolymers of poly(stearyl methacrylate)-b-poly(N-isopropylacrylamide)-b-poly(stearyl methacrylate) (PSMA-b-PNIPAAm-b-PSMA) with different molecular weights was synthesized through carboxyl-terminated trithiocarbonates as a highly efficient RAFT agent via reversible addition-fragmentation chain transfer (RAFT) polymerization. The resultant polymers were characterized by 1H NMR, FT-IR spectroscopy, and GPC. By varying the organic solvent used in the self-assembly procedure and adjusting the copolymer composition, multiple morphologies ranging from vesicles and core-shell spherical aggregates with different dimensions to pearl-necklace-like aggregates were obtained. The aggregates showed thermoresponsive and pH-responsive properties through the lower critical solution temperature (LCST) of PNIPAAm and the two carboxyl end groups of the copolymer.     

Thermally induced changes in amphiphilicity drive reversible restructuring of assemblies of ABC triblock copolymers with statistical polyether blocks

ABC triblock copolymers in which a block with stimulus-dependent solvophilicity resides between solvophilic and solvophobic end blocks can undergo reversible transitions between different thermodynamically stable assemblies in the presence or absence of stimulus. As a new example of such a copolymer system, thermoresponsive poly(ethylene oxide)-b-poly(ethylene oxide-stat-butylene oxide)-b-poly(isoprene) (E-BE-I) triblock copolymers with narrow molecular weight distributions (M(w)/M(n): 1.05-1.18) were prepared by sequential living anionic and nitroxide-mediated radical polymerizations. The specific copolymers examined (9.0 ≤ M(n) ≤ 14.4 kg/mol, 14% ≤ wt % isoprene ≤35%) form near-spherical aggregates with narrow size distributions at 25 °C. The thermoresponsive behavior of these polymers was studied by applying cloud point, DLS, and TEM measurements to a representative polymer, E(2.3)BE(5.3)I(2.3). The transformation of polymer aggregates from spherical micelles to vesicles (polymersomes) at elevated temperatures was detected by DLS and TEM studies, both with and without cross-linking of polymer assemblies. The rate of transformation with E-BE-I systems is more rapid than that observed for poly(ethylene oxide)-b-poly(N-isopropylacrylamide)-b-poly(isoprene) assemblies, suggesting that interchain hydrogen bonding of responsive blocks after dehydration plays an important role in the kinetics of aggregate rearrangement.     

Facile strategy for synthesis of silica/polymer hybrid hollow nanoparticles with channels

The silica/polymer hybrid hollow nanoparticles with channels and gatekeepers were successfully fabricated with a facile strategy by using thermoresponsive complex micelles of poly(ethylene glycol)-b-poly(N-isopropylacrylamide) (PEG-b-PNIPAM) and poly(N-isopropylacrylamide)-b-poly(4-vinylpyridine) (PNIPAM-b-P4VP) as the template. In aqueous solution, the complex micelles (PEG-b-PNIPAM/PNIPAM-b-P4VP) formed with the PNIPAM block as the core and the PEG/P4VP blocks as the mixed shell at 45 °C and pH 4.0. After shell cross-linking by 1,2-bis(2-iodoethoxyl)ethane (BIEE), tetraethylorthosilicate (TEOS) selectively well-deposited on the P4VP block and processed the sol-gel reaction. When the temperature was decreased to 4 °C, the PNIPAM block became swollen and further soluble, and the PEG-b-PNIPAM block copolymer escaped from the hybrid nanoparticles as a result of swelled PNIPAM and weak interaction between PEG and silica at pH 4.0. Therefore, the hybrid hollow silica nanoparticles with inner thermoresponsive PNIPAM as gatekeepers and channels in the silica shell were successfully obtained, which could be used for switchable controlled drug release. In the system, the complex micelles, as a template, could avoid the formation of larger aggregates during the preparation of the hybrid hollow silica nanoparticles. The thermoresponsive core (PNIPAM) could conveniently control the hollow space through the stimuli-responsive phase transition instead of calcination or chemical etching. In the meantime, the channel in the hybrid silica shell could be achieved because of the escape of PEG chains from the hybrid nanoparticles.