Vesicles Formed by Oligostyrene‐block‐Oligoaniline‐block‐Oligostyrene Triblock Oligomer

Novel π‐conjugated coil–rod–coil triblock oligomers containing optoelectronic active oligoaniline segments were synthesized. The block oligomer can self‐assemble into diverse aggregating morphologies including spherical micelles and thin‐layer vesicles in THF, which is found associated with the removing of the protecting groups of oligoaniline segments. A possible mechanism was proposed to explain the self‐assembly behavior changes in which chain conformation variation of the aniline segments initiated from deprotection of the nitrogen atoms is pointed to be the key factor that dominates the transition process.

     

Synthesis of Linear ABC Triblock Copolymers and Their Self‐Assembly in Solution

The self‐assembly of amphiphilic block copolymers has attracted the interest of a large number of research groups in the past two decades. Many examples have been reported using AB diblock copolymers, but the self‐assembly becomes more complex and shows a greater variety if ABC triblock copolymers are used. However, the synthesis of the polymer becomes more demanding since end‐group modifications or chain extensions become necessary. Using various kinds of polymerization techniques, pure triblock copolymers have been reported and their synthesis is covered in this review. Following the synthesis, a detailed and thorough analysis of the self‐assembly behaviour is the next step. We have selected promising and well characterized examples to show the range of self‐assembled structures possible, covering novel shapes of micelles but also polymersomes with an asymmetric membrane. Our selection of current examples in literature show the challenges and chances associated with amphiphilic ABC triblock copolymers.     

Multi‐Morphological Complex Aggregates Formed from Amphiphilic Poly(ethylene oxide)‐block‐Polydimethylsiloxane‐block‐Poly(ethylene oxide) Triblock Copolymers

Summary: Amphiphilic triblock copolymers (PEO_x‐b‐PDMS_y‐b‐PEO_x) with different block lengths were synthesized and multi‐morphological complex crew‐cut, star‐like, and short‐chain aggregates were prepared by self‐assembly of the given copolymers. The morphologies and dimensions of the aggregates can be well controlled by variation of the preparation conditions. TEM, SEM, FFR‐TEM, and LLS studies show the resulting morphologies range from LCMs, unilamellar or multilayer vesicles, LCVs, porous spheres to nanorods.

TEM images of the vesicles formed from PEO‐b‐PDMS‐b‐PEO.     

新型温度/pH敏感性ABA型三嵌段共聚物的合成、胶束化及凝胶化行为研究

采用原子转移自由基聚合（ATRP）方法合成了水溶性良好的不同聚合度的三嵌段共聚物P（DEAEMA-co-MEO₂MA-co-HMAM）-b-PEG-b-P（DEAEMA-co-MEO₂MA-co-HMAM）. 利用傅里叶变换红外光谱（FT-IR）、核磁共振氢谱（¹H NMR）以及凝胶渗透色谱（GPC）对聚合物结构及组成进行表征;通过透光率、表面张力的测定以及动态光散射（DLS）、荧光探针和透射电镜（TEM）技术研究了共聚物水溶液的性质及胶束化行为. 通过对不同pH下共聚物的凝胶状态和不同pH下温度诱导的溶胶-凝胶转变过程的观察,研究了温度和pH对共聚物凝胶化行为的影响. 测定了载药凝胶分别在不同温度和不同pH的缓冲溶液中对药物的累积释放率. 结果表明：ABA型三嵌段共聚物具有良好的温敏性和pH敏感性,在温度或pH诱导下可形成核壳胶束和凝胶. 载药凝胶对药物的累积释放率随温度和pH的降低而升高.     

Thermosensitive Nanoparticles Self‐Assembled from PCL‐b‐PEO‐b‐PNIPAAm Triblock Copolymers and their Potential for Controlled Drug Release

Thermosensitive nanoparticles with a core‐shell structure were prepared by self‐assembly of PCL‐b‐PEO‐b‐PNIPAAm triblock copolymers, which were synthesized by anionic ring‐opening polymerization and reversible addition fragmentation chain transfer (RAFT) polymerization. At temperatures above the lower critical solution temperature (LCST), the collapse of PNIPAAm chains in the outer shell and in the core of nanoparticle caused a decrease in size, while the constantly hydrophilic PEO chains in the shell endowed nanoparticles with excellent stability in water. The release of doxorubicin from these nanoparticles showed that both the length of PNIPAAm chains and temperature have great influence on drug release, which indicates the great potential of thermosensitive nanoparticles as drug carriers.

     

Multiple Sol‐Gel Transitions of PEG‐PCL‐PEG Triblock Copolymer Aqueous Solution

An aqueous solution of a poly(ethylene glycol)‐polycaprolactone‐poly(ethylene glycol) (PEG‐PCL‐PEG) with a composition of EG₁₃CL₂₃EG₁₃ undergoes multiple transitions, from sol‐to‐gel (hard gel)‐to‐sol‐to‐gel (soft gel)‐to‐sol, in the concentration range 20.0∼35.0 wt.‐%. Through dynamic mechanical analysis, UV‐vis spectrophotometry, small angle X‐ray scattering, differential scanning calorimetry, microcalorimetry and ¹³C NMR spectroscopy, the mechanism of these transitions was investigated. The hard gel and soft gel are distinguished by the crystalline and amorphous state of the PCL. The extent of PEG dehydration and the molecular motion of each block also played a critical role in the multiple transitions. This paper suggests a new mechanism for these multiple transitions driven by temperature changes.

     

Effect of PLGA block molecular weight on gelling temperature of PLGA‐PEG‐PLGA thermoresponsive copolymers

Thermoresponsive, biodegradable polymeric hydrogel networks are used widely in medicinal applications. Poly(d ,l ‐lactic acid‐co‐glycolic acid)‐b‐poly(ethylene glycol)‐b‐poly(d ,l ‐lactic acid‐co‐glycolic acid) (PLGA‐PEG‐PLGA) triblock copolymers exhibit a sol–gel transition upon heating. The effect of PLGA block and PEG chain molecular weights (MWs) on the gelling temperature of polymer aqueous solution (20% w/w) is described. All polymer solutions convert into a hard gel within 2 °C of the gelling temperature. The release properties of the gels were displayed using paracetamol as a representative drug. A linear relation is described between the gelling temperature and PLGA block MW. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 35–39     

Controlled Aqueous Solution Synthesis of Platinum–Palladium Alloy Nanodendrites with Various Compositions Using Amphiphilic Triblock Copolymers

In a recent study, we demonstrated that Pluronic F127 triblock copolymer plays a critical role in the formation of dendritic Pt nanostructures (L. Wang, Y. Yamauchi, J. Am. Chem. Soc. 2009 , 131, 9152–9153). Herein, we expand this concept to produce novel dendritic Pt–Pd alloy nanoparticles. In this paper, a very simple, one‐step and efficient route is proposed to directly produce dendritic Pt–Pd alloy nanoparticles with high surface area in high yield, which is carried out simply by stirring an aqueous solution that contains K₂PtCl₄ and Na₂PdCl₄ binary precursors in the presence of Pluronic F127 block copolymer and ascorbic acid at room temperature within 30 min without the need for any template, seed‐mediated growth, or additive. By simply changing the compositional ratios of the Pt and Pd sources in the precursor solutions, Pt–Pd nanodendrites with various compositions can be easily produced. Because of its unique simplicity, the proposed approach can be considered as a powerful strategy for producing Pt–Pd alloy nanoparticles with unique nanoarchitectures for commercial devices.     

Heteroarm Star‐Like Micelles Formed from Polystyrene‐block‐poly(2‐vinyl pyridine)‐block‐poly(methyl methacrylate) ABC Triblock Copolymers in Toluene

Polystyrene‐block‐poly(2‐vinyl pyridine)‐block‐poly(methyl methacrylate) ABC triblock copolymers were synthesized by sequential living anionic polymerization. Their solution properties were investigated in toluene, which is a bad solvent for the middle block. Spherical micelles are formed, which consist of a poly(2‐vinyl pyridine) dense core bearing polystyrene and poly(methyl methacrylate) soluble chains at the corona. These micelles exhibit the architecture of heteroarm star copolymers obtained by “living” polymerization methods. The aggregation numbers strongly depend on the length of the insoluble P2VP middle block, thus remarkably affecting the size of the micelles.     

Amphiphilic Seven-arm Star Triblock Copolymers with Diverse Morphologies in Aqueous Solution Induced by Crystallization and pH

Well-defined amphiphilic seven-arm star triblock copolymers containing hydrophobic crystalline poly(ε-caprolactone)(PCL) blocks, hydrophobic non-crystalline poly(tert-butyl acrylate)(PtBA) blocks and hydrophilic poly(ethylene glycol)(PEG) blocks were precisely synthesized by a combination of ring-opening polymerization(ROP), atom transfer radical polymerization(ATRP) and “click” reaction. Such star copolymers could self-assemble into “core-shell-corona” micelles and “multi-layer” vesicles depending on the fraction of each block. Meanwhile, the selective hydrolysis of middle PtBA blocks into the poly(acrylic acid)(PAA) blocks allowed the star block copolymers to further change their morphologies of aqueous aggregates in response to pH values.     

三嵌段共聚物和两嵌段共聚物在水溶液中共混自组装成多室胶束结构的耗散粒子动力学模拟(英文)

利用耗散粒子动力学模拟研究了在水溶液中混合不同的线形三嵌段共聚物AxByCz和线形两嵌段共聚物AmBn对多室胶束的形貌多样性的影响.通过改变线形的三嵌段共聚物和两嵌段共聚物的链长来寻找多室胶束的形成条件.由线形三嵌段共聚物和线形两嵌段共聚物的不同混合形成的多室胶束结构是多种多样的,例如"蠕虫状"胶束、"汉堡包"胶束、"球上球"胶束、"核-壳-壳"胶束等等.多室胶束的整体形貌和内部结构的控制都可以从线形三嵌段共聚物和两嵌段共聚物的二元共混得到.为了表征获得的多室胶束结构,我们计算了密度图和成对分布函数图.在此工作中,可以获得和观察到复杂的多室胶束.结果表明,简单地混合线形的三嵌段共聚物和线形的两嵌段共聚物是一个控制多室胶束形貌和结构的有效方法,在工程实验中可以更简单更经济地形成多室胶束结构.因此,在设计新的多室胶束方面,聚合物共混仍然是未来值得更加关注的一个话题.     

Synthesis and Preliminary Biological Evaluation of Novel Functionalised Poly(ethylene glycol)‐block‐poly(ester‐carbonate) Copolymers as Biodegradable Polymeric Carriers

Polymer conjugates of anticancer drugs containing bound active moieties are used to improve pharmacokinetics by prolonging antitumour activity and decreasing protein immunogenicity. The first generation of polymer conjugates, N‐(2‐hydroxylpropyl)methacrylamide copolymer or poly(ethylene glycol) conjugates, cannot be considered optimised since their polymer chain lacks biodegradability. The polymeric system proposed here is based on high molecular weight water‐soluble functionalised polyesters containing fumarate or maleate units linked by poly(ethylene glycol) segments by means of carbonate bonds. It shows the following features: a) high molecular weight; b) biodegradable backbone (rate of degradation was determined viscometrically in vitro, under conditions mimicking physiological conditions and c) water solubility. Also the biocompatibility of the polymer and its precursors were assessed using a B16F10 murine melanoma cell line and a haemolysis assay.     

Biodegradable Self‐Assembled Nanoparticles of Galactose‐Containing Amphiphilic Triblock Copolymers for Targeted Delivery of Paclitaxel to HepG2 Cells

Biodegradable self‐assembled polymeric nanoparticles (NPs) composed of poly(6‐O‐methacryloyl‐D‐galactopyranose)‐b‐poly(L‐lactide)‐b‐poly(6‐O‐methacryloyl‐D‐galactopyranose) (PMAGP‐b‐PLA‐b‐PMAGP) are prepared as carriers for the hydrophobic anticancer drug paclitaxel (PTX), to achieve target delivery to hepatoma cells. PTX can be encapsulated by the NPs with various molar ratios of L‐lactide (LA) and 6‐O‐methacryloyl‐D‐galactopyranose (MAGP) during the process of self‐assembly, and the resulting NPs exhibit high drug loading efficacy and substantial stability in aqueous solution. The size, size distribution, and morphology of the NPs are characterized using a Zetasizer Nano ZS and transmission electron microscopy. The hemolysis assay and cell cytotoxicity assay indicate that the polymeric NPs are biocompatible and non‐toxic. The cellular uptake assay demonstrates that the galactose‐containing NPs can be selectively recognized and subsequently accumulate in HepG2 cells. All of these results demonstrate that galactose‐containing polymeric NPs are potential carriers for hepatoma‐targeted drug delivery and liver cancer therapy in clinical medicine.

     

Interactions of Ionic Surfactants With PEO-PBO-PEO Triblock Copolymers in Aqueous Solutions

The interactions of triblock copolymers (TBP) with ionic surfactants were studied employing surface tensiometry, electrical conductivity, steady-state fluorescence (SSF), and dynamic light scattering (DLS) techniques. An increasing trend in the critical micelle concentration (CMC) of SDS/CTAB in the presence of triblock copolymers was observed especially at higher polymer to surfactant ratio. The delay in the CMC of surfactants was more pronounced in the presence of E₄₈B₁₀E₄₈ possibly due to its less hydrophobic nature. The negative values of free energy of micellization (ΔG_m) both in case of SDS and CTAB confirmed the spontaneity of the processes. The aggregation number (N_agg) and hydrodynamic radius (R_h) of polymer/surfactant mixed systems were determined by SSF and DLS. The suppression of the surfactant micelle size in the presence of TBP was confirmed by SSF and DLS studies.     

pH响应性ABC型共聚物的合成与溶液自组装

用单氨基聚乙二醇(m PEG-NH2)引发ε-三氟乙酰基-L-赖氨酸-N-羧酸酐(Lys(TFA)-NCA)开环聚合,得到了聚乙二醇-b-聚(ε-三氟乙酰基-L-赖氨酸)(PEG-b-PTLL)两嵌段共聚物.将PTLL链段末端的NH2与2-溴异丁酰溴反应得到了大分子引发剂,通过原子转移自由基聚合(ATRP)的方法分别分别引发苯乙烯(St)和N-异丙基丙烯酰胺(NIPAM)聚合,制备了结构明确、聚合度可控的聚乙二醇-b-聚(ε-三氟乙酰基-L-赖氨酸)-b-聚苯乙烯(PEG-b-PTLL-b-PS)和聚乙二醇-b-聚(ε-三氟乙酰基-L-赖氨酸)-b-聚(N-异丙基丙烯酰胺)(PEG-b-PTLL-b-PNIPAM)三嵌段杂化共聚肽.将PEG-b-PTLL-b-PNIPAM去保护后得到温度和p H响应三嵌段共聚物;将PEG-b-PTLL-b-PS去保护后得到p H响应的两亲性三嵌段共聚物.研究了PEG45-b-PLL106-b-PS20在混合溶剂H2O/DMF中的p H诱导胶束化行为.TEM结果表明,当水溶液p H小于PLL的p Ka时,PEG45-bPLL106-b-PS20形成球状胶束,当水溶液p H大于PLL的p Ka时,PLL转变成α-螺旋,PEG45-b-PLL106-b-PS20组装成盘状胶束.     

官能化聚四氢呋喃-b-聚异丁烯-b-聚四氢呋喃三嵌段共聚物的合成与性能

采用2-氯-2,4,4-三甲基戊烷或对二枯基氯为引发剂和TiCl4或FeCl3为共引发剂,引发异丁烯(IB)可控/活性正离子聚合与官能端基转化,设计合成不同分子量及窄分子量分布的端基官能化聚异丁烯,如双端烯丙基溴官能化聚异丁烯(Br-PIB-Br)或双端烯丙基胺官能化聚异丁烯(H2N-PIB-NH2).采用烯丙基溴/高氯酸银体系引发四氢呋喃(THF)开环聚合,合成聚四氢呋喃活性链(PTHF+).进一步通过将IB可控/活性正离子聚合与THF可控/活性正离子开环聚合2种方法相结合,设计合成2种新型官能化聚四氢呋喃-b-聚异丁烯-b-聚四氢呋喃(PTHF-b-PIB-b-PTHF)三嵌段共聚物:(1)以上述Br-PIB-Br为大分子引发剂,在AgClO4作用下引发THF活性正离子开环聚合,采用水终止活性链端,设计合成双端为羟基的HO-PTHF-b-PIB-b-PTHF-OH三嵌段共聚物(简称:FIBF-OH);(2)以上述合成的PTHF+活性链与H2NPIB-NH2链端胺基发生高效亲核取代反应,设计合成中间链段连接点含―NH―官能基团的PTHF-b-HNPIB-NH-b-PTHF三嵌段共聚物(简称:FIBF-NH).在上述三嵌段共聚物中,极性PTHF链段与非极性PIB链段的热力学不相容,导致其呈现明显的微相分离,且微观形态与共聚组成相关.PTHF均聚物易结晶,在上述共聚物中由于PTHF链段单端受限致其结晶性减弱.三嵌段共聚物分子链的中间连接点含―NH―官能基团,具有更强的氢键作用,促进PTHF链段重排并结晶,易形成更紧密的超分子网络结构,导致即使在PTHF链段相对分子量为0.7 kg·mol^-1时仍具有较强的结晶性,且结晶熔融温度明显提高.此外,由于FIBF-NH中形成超分子网络结构,使材料具有优异的自修复性能,材料表面的切痕在常温下10 min后可以完全自愈合.本文设计合成的新型官能化PTHF-b-PIB-b-PTHF三嵌段共聚物兼具有PTHF与PIB的优良性能,在生物医用、智能修复等功能材料领域具有潜在的应用前景.     

2,6‐Diaminopyridine and Acrylamide‐Based Copolymers with Upper Critical Solution Temperature‐type Behavior in Aqueous Solution

A novel copolymer based on supramolecular motif 2,6‐diaminopyridine and water‐soluble acrylamide, poly[N‐(6‐acetamidopyridin‐2‐yl) acrylamide‐co‐acrylamide], was synthesized via reversible addition–fragmentation chain transfer (RAFT) polymerization with various monomer compositions. The thermoresponsive behavior of the copolymers was studied by turbidimetry and dynamic light scattering (DLS). The obtained copolymers showed an upper critical solution temperature (UCST)‐type phase transition behavior in water and electrolyte solution. The phase transition temperature was found to increase with decreasing amount of acrylamide in the copolymer and increasing concentration of the solution. Furthermore, the phase transition temperature varied in aqueous solutions of electrolytes according to the nature and concentration of the electrolyte in accordance with the Hoffmeister series. A dramatic solvent isotope effect on the transition temperature was observed in this study, as the transition temperature was almost 10–12 °C higher in D₂O than in H₂O at the same concentration and acrylamide composition. The size of the aggregates below the transition temperature was larger in D₂O compared to that in H₂O that can be explained by deuterium isotope effect. The thermoresponsive behavior of the copolymers was also investigated in different cell medium and found to be exhibited UCST‐type phase transition behavior in different cell medium. Such behavior of the copolymers can be useful in many applications including biomedical, microfluidics, optical materials, and in drug delivery. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2064–2073     

Polyglycidol Based Amphiphilic Double‐Comb Copolymers and Their Self‐Association in Aqueous Solution

Herein, we report synthesis and self‐association properties of amphiphilic double‐comb polymers with polyglycidol backbones. First, a bifunctional polyglycidol precursor is synthesized via monomer activated anionic polymerization. Next, two efficient and orthogonal polymer analogous reactions are carried out for grafting hydrophilic oligoethylene glycol side chains and hydrophobic linear aliphatic side‐chains. The polymers are analyzed by means of NMR, GPC, and DSC. From the DSC analysis of the bulk samples it is evident that aliphatic side chains segregate from the polar backbone and thus crystallize. Furthermore, in aqueous media the double‐comb polymers spontaneously self‐assemble to form a multilayer structure. The present results pave a way to tailor and design amphiphilic polymers based on glycidols. Major advantages are spontaneous self‐assembly in water and the possibility to form onion polymersomes relevant to encapsulation.