Pod-Like Supramicelles with Multicompartment Hydrophobic Cores Prepared by Self-Assembly of Modified Chitosan

In this paper, pod-like supramicelles with multicompartment hydrophobic cores were prepared by selfassembly of amphiphilic N-phthaloylchitosan-g-poly(N-vinylcaprolactam)(PHCS-g-PNVCL) in aqueous medium. The employed biocompatible amphiphilic polymer was synthesized by grafting the carboxyl terminated poly(N-vinylcaprolactam)(PNVCL-COOH) chains onto N-phthaloylchitosan(PHCS) backbone.~1H NMR and FTIR results confirmed the molecular structure of the copolymers. The morphology of the supramicelles assembled by PHCS-g-PNVCL was revealed by means of TEM and polarized light microscope. In solution, the supramicelles were very stable as monitored by DLS and zeta potential measurements. Temperature and p H presented significant influences on the size and size distribution of the supramicelles. These supramicelles with multicompartment hydrophobic cores should be ideal biomimetic systems with promising applications in drug delivery.

Linear-like polypeptide-based micelle with pH-sensitive detachable PEG to deliver dimeric camptothecin for cancer therapy

Nano drug delivery systems have made significant progress in delivering anticancer drugs camptothecin(CPT).However,many challenges for CPT delivery remain,including low drug loading efficiency,premature drug leakage,and poor cellular internalization.Herein,we report a novel dual-sensitive polypeptide-based micelle with remarkably high drug loading of CPT for cancer therapy.This self-assembled micelle possesses the following essential components for CPT:(1)pH-sensitive PEG(OHC-PEG-CHO)for prolonging blood circulation and allowing biocompatibility by shielding the cationic micelles,which can be detached under the tumor acidic microenvironment and facilitates the cellular uptake;(2)polypeptide polylysine-polyphenylalanine(PKF)synthesized via ring-opening polymerization for micelle formation and CPT analogue loading;(3)dimeric CPT(DCPT)with redox-sensitive linker for increasing CPT loading and ensuring drug release at tumor sites.Interestingly,the linear-like morphology of PEG-PKF/DCPT micelles was able to enhance their cellular internalization when compared with the spherical blank PKF micelles.Also,the anticancer efficacy of DCPT against lung cancer cells was significantly improved by the micelle formation.In conclusion,this work provides a promising strategy facilitating the safety and effective application of CPT in cancer therapy.

FORMATION OF FLOWER-LIKE AGGREGATES FROM SELF-ASSEMBLING OF MICELLES WITH PEO SHELLS AND CROSS-LINKED POLYACRYLAMIDE CORES

Amphiphilic block copolymers,poly(ethylene oxide)-b-poly(N-acryloxysuccinimide) (PEO-b-PNAS) with various molecular weights have been successfully synthesized by atom transfer radical polymerization (ATRP) of NAS using functionalized PEO (PEO-Br) as ATRP macroinitiator.The self-assembling of the block copolymers in water,which is a good solvent for PEO and a non-solvent for PNAS.yielded spherical core-shell micelles with PNAS as core and PEO as shell.The cross-linked reaction of oxysuccinimide in PNAS chain...

SELF-ASSEMBLING AMPHIPHILIC POLYELECTROLYTES AND THEIR NANOSTRUCTURES

The self-assembling behavior of random copolymers of sodium 2-(acrylamido)-2-methylpropanesulfonate (AMPS)and hydrophobic comonomers possessing dodecyl groups linked by various spacer bonds was discussed with a focus on theeffect of the spacer. The characterization of association behavior of such polymers in water using quasielastic light scattering,capillary electrophoresis, NMR relaxation, various fluorescence, and viscoelastic methods was described. These copolymersform a variety of self-assembled nanostructures depending on the type of the spacer. Random copolymers of AMPS and N-dodecylmethacrylamide show a strong preference for intrapolymer self-association even in concentrated aqueous solutionsforming single-macromolecular self-assemblies (unimolecular micelles). In contrast, random copolymers of AMPS anddodecyl methacrylate are prone to undergo interpolymer associations yielding multipolymer micelles. In random copolymersof AMPS and a methacrylate substituted a nonionic surfactant (HO(CH_2CH_2O)_(25)C_(12)H_(25)) (C_(12)E_(25)), dodecyl groups are muchless restricted by the polymer backbone because they are linked via a long, flexible hydrophilic spacer. Thus, the polymer-bound C_(12)E_(25) surfactant moieties form micelles similar to those formed by discrete surfactants, but they are bridged bypolymer chains forming a network structure.

Tumor-targeted self-assembled micelles reducing PD-L1 expression combined with ICIs to enhance chemo-immunotherapy of TNBC

Immune checkpoint inhibitors(ICIs)therapy targeting programmed cell death ligand 1(PD-L1)and programmed death protein 1(PD-1)had exhibited significant clinical benefits for cancer treatment such as triple negative breast cancer(TNBC).However,the relatively low anti-tumor immune response rate and ICIs drug resistance highlight the necessity of developing ICIs combination therapy strategies to improve the anti-tumor effect of immunotherapy.Herein,the immunomodulator epigallocatechin gallate palmitate(PEGCG)and the immunoadjuvant metformin(MET)self-assembled into tumor-targeted micelles via hydrogen bond and electrostatic interaction,which encapsulated the therapeutic agents doxorubicin(DOX)-loaded PEGCG-MET micelles(PMD)and combined with ICIs(anti-PD-1 antibody)as therapeutic strategy to reduce the endogenous expression of PD-L1 and improve the tumor immunosuppressive microenvironment.The results presented that PMD integrated chemotherapy and immunotherapy to enhance antitumor efficacy in vitro and in vivo,compared with DOX or anti-PD-1 antibody for the therapy of TNBC.PMD micelles might be a potential candidate,which could remedy the shortcomings of antibody-based ICIs and provide synergistic effect to enhance the antitumor effects of ICIs in tumor therapy.

Intermolecular Interactions in Self-Assembly Process of Sodium Dodecyl Sulfate by Vertically Polarized Raman Spectra

Molecular self-assembly is extremely important in many fields, but the characterization of their corresponding intermolecular interactions is still lacking. The C-H stretching Raman band can reflect the hydrophobic interactions during the self-assembly process of sodium dodecyl sulfate （SDS） in aqueous solutions. However, the Raman spectra in this region are seriously overlapped by the OH stretching band of water. In this work, vertically polarized Raman spectra were used to improve the detection sensitivity of spectra of C-H region for the first time. The spectral results showed that the first critical micelle concentration and the second critical micelle concentration of SDS in water were 8.5 and 69 mmol/L, respectively, which were consistent with the results given by surface tension measurements. Because of the high sensitivity of vertically polarized Raman spectra, the critical micelle concentration of SDS in a relatively high concentration of salt solution could be obtained in our experiment. The two critical concentrations of SDS in 100 mmol/L NaCl solution were recorded to be 1.8 and 16.5 mmol/L, respectively. Through comparing the spectra and surface tension of SDS in water and in NaCl solution, the self-assembly process in bulk phase and at interface were discussed. The interactions among salt ions, SDS and water molecules were also analyzed. These results demonstrated the vertically polarized Raman spectra could be employed to study the self-assembly process of SDS in water.

Formation of Copolymer-Ag Nanoparticles Composite Micelles in Three-dimensional Co-flow Focusing Microfluidic Device

A novel method was presented to create composite micelles of amphiphilic copolymers and Ag nanoparticles(NPs) in a three-dimensional co-flow focusing microfluidic device(3D CFMD). Self-assembly of the copolymers was initiated by the fast mixing of water and a blend dispersion of hydrophobic Ag NPs and amphiphilic copolymers. At the same time, the hydrophobic Ag NPs enter the core of copolymer micelles, based on the hydrophobic interaction. The copolymer-Ag NPs composite micelles have a core-shell structure with copolymer shell and Ag NPs core. COMSOL Multiphysics is used to simulate the concentration distribution of copolymers and Ag NPs under different flow rates. Co-assembly microfluidic conditions are determined based on simulation results. Under suitable microfluidic conditions, both block copolymers and gradient copolymers can co-assemble with hydrophobic Ag NPs to form composite micelles, respectively. This microfluidic coassembly method will have a good prospect in the preparation of composite micelles of amphiphilic copolymers and metal nanoparticles.

Polymeric complex micelle loaded with axially substituted silicon(Ⅳ) phthalocyanine

A novel axially substituted silicon（IV） phthalocyanine, namely di-pyridyloxy axially substituted silicon（IV） phthalocyanine 2 was synthesized and characterized by UV/vis, IR, elemental analysis, MS as well as IH NMR spectroscopy. Hydrophobic 2 was encapsulated by amphiphilic triblock copolymer poly[N^e-（benzyloxycarbonyl-lysine]-poly（ethylene glycol）-poly [N^e-（benzyl oxycarbonyl） （PLL（Z）-b-PEG-b-PLL（Z）） to form hydrophobic 2-loaded polymeric complex micelle （PIC） （2-loaded P/C）. Atom force microscopy （AFM） image showed that 2-loaded PIC formed a spherical nanocarrier with approximately 35-50 nm in diameter. The fluorescence intensity and lifetime of 2-loaded PIC was significantly enhanced bv the incorporation 2 into PIC nanocarrier.

Synthesis and characterization of a novel amphiphilic biodegradable β-cyclodextrin/poly(γ-benzyl L-glutamate) copolymer

β-Cyclodextrin/poly（γ-benzyl L-glutamate） （β-CD-PBLG） copolymers were synthesized by ring-opening polymerization of N- carboxy-γ-benzyl L-glutamate anhydride （BLG-NCA） in N,N-dimethylformamide （DMF） initiated by mono-amino-β-cyclodextrin（H2N-β-CD）. The structures of the copolymers were confirmed by IR, ^1H NMR and GPC. The fluorescence technique was used to determine the critical micelle concentrations （CMC） of copolymer micell solution, the diameter and the distribution of micelles were characterized by DLS. The results showed that BLG-NCA could be initiated by H2N-β-CD to produce copolymer. The nanomicells were formed by these copolymers in water.

MORPHOLOGICAL TRANSITION BETWEEN VESICLES AND TUBULES FOR A GLYCOPOLYMER-CONTAINING AMPHIPHILIC DIBLOCK COPOLYMER IN AQUEOUS SOLUTIONS

The morphological transition of molecular assemblies in aqueous solutions for a new amphiphilic diblock copolymer induced by changing the initial solvent conditions was studied by transmission electron microscopy (TEM). The copolymer was polystyrene(77)-b-poly[2-(beta -D-glucopyranosyloxy)ethyl acrylate (6)] (PSt(77)-b-PGEA(6)) and the solvent was a mixture of DMF and THF. PSt(77)-b-PGEA(6) yields vesicles and tubules when it is initially dissolved in THF and DMF respectively. The morphological transition between vesicles and tubules can be achieved by simply varying the amounts of THF and DMF, or changing the temperature at which the aggregates were prepared.

Synthesis and Immobilization of Polystyrene-b-Polyvinyltriethoxysilane Micelles

Diblock copolymers polystyrene-block-polyvinyltriethoxysilane（PS-b-PVTES） were synthesized via atom transfer radical polymerization（ATRP）, which self-assembled into spherical micelles in solvent of THF-methanol mixtures. The self-assembled micelles were immobilized by cross-linking reaction of VTES in a shell layer of micelles. The chemical structures of block copolymers and morphology of micelles were characterized in detail. It was found that the size of immobilized micelles was strongly affected by the copolymer concentration, composition of mixture solvent, and block ratios.

SYNTHESIS OF A NOVEL AMPHIPHILE, 4-[4-(4-DECYLOXYPHENYLAZO) NAPHTHYLOXY] BUTYL TRIMETHYLAMMONIUM BROMIDE, AND ITS SELF-ASSEMBLING BEHAVIOR IN DILUTE AQUEOUS SOLUTION

A novel amphiphile of 4-[4-(4-decyloxyphenylazo) naphthyloxy] butyl trimethylammonium bromide has been synthesized. It can form the stable bilayer in dilute aqueous solution.

Polyamine-Polymeric Micelle Hybrid Hydrogel: Microscopic Properties of Crosslinkers Affecting Macroscopic Rheological Properties of Hydrogel

We have developed a hybrid hydrogel that is formed from a crosslinkable polymeric micelle and a polyamine. Under optimal conditions, the hydrogel rapidly formed in one second after a crosslinkable polymeric micelle solution was mixed with a polyamine solution. We could change the hydrogel’s gelation properties, such as the storage modulus and gelation time by tuning the molecular weights of block copolymers and by tuning the pH of the dissolving-solvent of the hydrogel’s constituent components. Furthermore, we have clarified here that the structural difference among the micelles acting as crosslinkers can affect the gelation properties of the hydrogel. According to our findings, the hydrogel that was formed from the polymeric micelles possessing a highly packed (i.e., well-entangled or crosslinked) inner core exhibited a higher storage modulus than the hydrogel that was formed from the polymeric micelles possessing a lowly packed structure. Our results demonstrate that a microscopic structural difference among crosslinkers can induce a macroscopic change in the properties of the resulting hydrogels. For medical applications, the hydrogel proposed in the present paper can encapsulate the hydrophobic compounds in crosslinkers (polymeric micelles) so that the hydrogel can be available as the biomaterial for their sustained release.

An amphiphilic[2]biphenyl-extended pillar[6]arene:Synthesis,controllable self-assembly in water and application in cell-imaging

Synthesis and functionalization of novel macrocyclic host molecules are important topics in supramolecular chemistry.In this work,the first amphiphilic[2]biphenyl-extended pillar[6]arene(AM-[2]BP-ExP6)was designed and synthesized with poly(ethylene glycol)chains as the hydrophilic tails and a rigid cavity as the hydrophobic core.Due to its amphiphilic nature,AM-[2]BP-ExP6 could self-assemble to stable fibers in water.What’s more,AM-[2]BP-ExP6 could associate with quaternary ammonium modified tetraphenylethylene guest(QTPE)to form a 2:1 host-guest complex,accompanied by significant enhanced fluorescence.Interestingly,different like AM-[2]BP-ExP6,AM-[2]BP-ExP6⊃QTPE host-guest complex selfassembled into fluorescent particles with diameter about 310 nm,the obtained fluorescent particles can be further employed in living cell imaging.

聚醚型两亲分子对水泥净浆收缩的影响及机理

将5种聚醚型两亲分子作为减缩组分,测试了其对水泥净浆收缩变形的影响,探究了表面张力与胶束粒径分布对收缩的影响机理.结果表明:二乙二醇丁醚、三丙二醇甲醚和聚乙二醇400不形成稳定的胶束,减缩效果随着孔溶液表面张力的降低而提高;聚醚改性硅油具有低临界胶束浓度(CMC),形成的胶束大小为30 nm左右,影响了聚醚改性硅油单体在毛细孔溶液表面的铺展,同时细化了水泥石的孔结构,减缩效果较差;含氟聚醚具有超低的表面张力及CMC,其胶束易产生聚沉,孔溶液的有效含量极低,无减缩效果.

均聚物的添加对棒/线两亲性嵌段共聚物溶液自组装的影响

为了明晰均聚物对棒/线嵌段共聚物聚集行为的影响,利用实空间求解的格子自洽场方法,研究柔性均聚物和线/棒/线两亲性对称三嵌段共聚物溶液混合体系的自组装行为.格子自洽场方法通过链传播子和格子的各向异性近似处理分子链刚性,这使得该方法在计算速度方面有显著优势.模拟结果表明,均聚物对胶束结构重排行为的影响依赖于疏水棒嵌段长度,这源于棒嵌段长度的改变一定程度上影响了胶束破碎/融合的实现.研究还发现,均聚物的添加稳定了胶束重排过程中胶束结构的变化.本文的结果有助于进一步理解以刚性嵌段为核心胶束的生长机制,为相关的实验设计和材料应用提供理论指导.

羧甲基纤维素棕榈酸酯的合成及其胶束包载姜黄素研究

以羧甲基纤维素和棕榈酸为原料,合成具有两亲性的羧甲基纤维素棕榈酸酯,以其在水相中自组装形成的胶束作为载体对姜黄素进行包载。通过红外光谱验证了羧甲基纤维素棕榈酸酯的成功合成,激光粒度仪测试则证明载药胶束纳米乳液的形成,采用液相色谱测试并计算了载药胶束的载药量及包封率。本研究以全生物基载体实现了疏水姜黄素在水中的稳定分散。

Preparation and self-assembly of amphiphilic polymer with aggregation-induced emission characteristics

An amphiphilic polymer bearing tetraphenylethene (TPE) moiety was synthesized by convenient reactions. The polymer exhibits unique aggregation-induced emission (AIE) characteristics and can self-assemble to size-tunable particles in DMF/water mixtures. The polymer nanoparticles can be used for cell imaging, which provides a potential stable fluorescent tool to monitor the distribution of drugs and bioconjugates in living cells.

Controlled Self-assembly of Thermo-responsive Amphiphilic H-shaped Polymer for Adjustable Drug Release

Despite the fact that some progress has been made in the self-assembly of H-shaped polymers, the corresponding self-assemblies that respond to external stimulus and are further utilized to adjust the release of drugs are still deficient. The stimuli-responsive segments with amphiphilic H-shaped structure are generally expected to enhance the controllability of self-assembly process. The synthesis and self-assembly behavior of thermo-responsive amphiphilic H-shaped polymers with poly（ethylene glycol） （PEG）, polytetrahydrofuran （PTHF） and poly（N-isopropyl acrylamide） （PNIPAM） as building blocks are reported in this paper. The inner architecture structure and size of complex micelles formed by H-shaped self-assemblies were effectively adjusted when the solution temperature was increased above the lower critical solution temperature of PNIPAM segments. Furthermore, it was found that the architecture of self-assemblies underwent a transition from the complex micelles based on primary micelles with hybrid PEG/PNIPAM shells to large complex micelles based on primary micelles with hybrid PTHF/PNIPAM cores and PEG shells during the thermal-induced self-assembly process. The adjustable release rate ofdoxorubicin （DOX） from the DOX-loaded complex micelles and basic cell experiments further proved the feasibility of these self-assemblies as the thermal-responsive drug delivery system.

Study on Thermosensitive Micellization of Dextran-g-PNIPAAm in Aqueous Solutions

The thermosensitive micellization of dextran-g-PNIPAAm in aqueous solutions has been investigated by fluorescence spectroscopy, dynamic light scattering and transmission electron microscope. The formed polymeric micelles showed different diameters of about 20 nm or 100 nm, when the solution temperature was below or above the phase transition temperature.