叶酸高分子纳米胶束在小鼠体内的靶向分布

合成了带有叶酸靶向和荧光染料的聚合物FA-PEG-PLA和mPEG-b-P（LA-co-MHC／NIR）,通过混合胶束的方法制备近红外染料胶束P（NIR）（含染料NIR6％）,叶酸胶束FA-P（NIR）1（含染料NIR5．4％,叶酸LFA0．5％）和叶酸胶束FA-P（NIR）2（含染料NIR4．8％,叶酸FA0．9％）;建立了H22肝癌小鼠模型,考察了高分子纳米胶束及叶酸靶向纳米胶束在H22肝癌小鼠体内分布．结果表明,高分子纳米胶束及叶酸靶向纳米胶束在小鼠体内分布都具有时间相关性,无叶酸配体的高分子纳米胶束在尾静脉注射24h后在肿瘤部位有少量聚集,大部分胶束在肝部聚集,30h内大部分已被排泄系统排出体外;含有叶酸配体的纳米胶束在尾静脉注射后6-30h内在肿瘤部位有明显的聚集,其中,FA-P（NIR）1胶束在肿瘤和肝部位的聚集相当,FA-P（NIR）2胶束在静脉注射24h后在肿瘤聚集明显高于肝部．带有叶酸配体的高分子纳米胶束相对于不带叶酸配体的纳米胶束在小鼠肿瘤部位具有明显的聚集,并且随着叶酸含量的增大,聚集效果更明显．     

Intact human holo-transferrin interaction with oxaliplatin

We report the interaction of intact human holo-transferrin (holo-Tf) with oxaliplatin (an anticancer drug), and the characterization of a complex composed of (1:1) intact holo-Tf and the parent oxaliplatin molecule using nanoelectrospray ionization quadrupole time-of-flight mass spectrometry (nanoESI-QTOF-MS). The molecular weight of this complex was determined to be 80,077 Da, which was an increase of 397 mass units compared to the protein alone (79,680 Da), suggesting that a parent drug molecule was bound to the intact protein. We further examined the interaction between the intact protein and oxaliplatin using size-exclusion high-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC/ICPMS). The protein complex and free oxaliplatin were separated by HPLC and quantitatively determined by simultaneous monitoring of both 195Pt and 56Fe using ICPMS. The HPLC/ICPMS detected both Pt and Fe signals at retention time of 2.6 min, identifying the protein-drug complex. The Fe signal at 2.6 min did not change with the increase in incubation time of the reaction mixture containing holo-Tf and oxaliplatin, while the Pt signal at the same retention time increased over time, further demonstrating that the formation of this complex does not affect the protein-bound Fe. The binding constant of the (1:1) intact human holo-Tf-oxaliplatin complex was determined to be 7.7x10(5) M-1. Both nanoESI-MS and HPLC/ICPMS results support that the holo-Tf and parent oxaliplatin molecules form complexes through non-covalent binding, suggesting that holo-Tf may be a useful carrier for oxaliplatin delivery.     

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 of doxorubicin (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.     

Pyranine-induced micellization of poly(ethylene glycol)-block-poly(4-vinylpyridine) and pH-triggered release of pyranine from the complex micelles

The pyranine-induced micellization of poly(ethylene glycol)-block-poly(4-vinylpyridine) (PEG114-b-P4VP61) in aqueous solutions and pH-triggered release of pyranine from the complex micelles were studied by dynamic and static light scattering, transmission electron microscopy, 1H NMR spectroscopy, and UV-vis spectroscopy. At pH 2, the ionized pyranine can ionically cross-link the protonated P4VP block and result in well-defined spherical complex micelles with a P4VP/pyranine core surrounded by a PEG corona. The ratio of pyranine to pyridyl units can influence the structure and the properties of the resultant complex micelles. The complex micelles are stable upon dilution and heating but are sensitive to pH changes. pH-triggered release of the incorporated pyranine from the complex micelles demonstrates that the release behavior is pH-tunable and displays good controlled-release characteristics at pH approximately 4.     

Enhanced stability of ZnTPPS by polymeric gold nanoparticles in acidic aqueous solutions

Novel kind of core-shell corona complex micelles were prepared, which enhanced both the hydrolytic stability and the photostability of water-soluble zinc tetrakis(4-sulfonatophenyl) porphyrin (ZnTPPS) in acidic aqueous solutions. The core-shell gold nanoparticles (AuNPS) were synthesized by reducing HAuCl₄ and di-thioester terminated block copolymer, poly(Nisopropylacrylamide)-block-poly(4-vinylpyridine) (PNIPAM-b-P4VP). The complex micelles with gold core, P4VP/ZnTPPS shell and PNIPAM corona were formed by simple mixing of gold nanoparticles and ZnTPPS. The photochemical properties of the complex micelles were studied by UV–Visiblespectroscopy and fluorescence spectroscopy. The results showed trapping of ZnTPPS in the positively charged micellar shell that effectively prevented demetallation of the ZnTPPS that would occur in acidic aqueous solutions. Furthermore, with appropriate concentration of gold nanoparticles, ZnTPPS in the complex micelle had excellent photostability by suppression of generation of reactive oxygen species (ROS). The enhanced stability of ZnTPPS in acidic aqueous media could be extensively used for photocatalysis and in solar cells.     

Assessment of the integrity of poly(caprolactone)-b-poly(ethylene oxide) micelles under biological conditions: a fluorogenic-based approach

The integrity of block copolymer micelles is important for their effectiveness and successful delivery of the incorporated drugs. Here we evaluate the integrity of poly(caprolactone)-b-poly(ethylene oxide) micelles in media of varying chemical complexity and in cells by using fluorogenic micelles. Fluorogenic dye fluorescein-5-carbonyl azide diacetate was covalently attached to the micelle-core-forming part of the block copolymer, poly(caprolactone). The fluorescence was not detectable unless the poly(caprolactone)21-b-poly(ethylene oxide)45 micelles were destroyed and the fluorogenic dye was activated by deesterification. The fluorescence of the activated dye from destroyed micelles was easily detectable in various media and in cells. Micelles were stable in simple media such as phosphate-buffered saline but disassembled to varying extents with increasing chemical complexity of the media and addition of serum. The integrity of the internalized micelles within the cells showed a time-dependent decrease but remained largely preserved (80%) after 20 h of incubation with cells. A proof of principle was also demonstrated in vivo in mice. The fluorogenic approach to micelle integrity assessment presented herein should lend itself to other block copolymer micelles and assessments of their integrity in complex biological systems in vitro and in vivo.     

Fabrication of biofunctional complex micelles with tunable structure for application in controlled drug release

In acidic solution, complex micelles were formed by diblock copolymers of poly (ethylene glycol)-b-poly (ε-caprolactone) (PEG-b-PCL) and folate-poly (2-(dimethylamino) ethyl methylacrylate)-b-poly (ε-caprolactone) (Fol-PDMAEMA-b-PCL) with a PCL core, a mixed PEG/Fol-PDMAEMA shell. The surface charge of the complex micelles was positive at acidic surroundings for the protonated PDMAEMA. With increasing pH value to 7.4 (above pK _a of PDMAEMA), these micelles could convert into a core-shell-corona (CSC) structure composing a hydrophobic PCL core, a collapsed PDMAEMA shell, and a soluble PEG corona. Compared to core-shell micelles formed by PEG-b-PCL, micelles with CSC structure can prolong degradation by enzyme. Doxorubicin was physically loaded into the PCL core. The drug release rate was pH-dependent. At pH 5.5, complex micelles with core-shell structure showed faster drug release rate, while at pH 7.4, complex micelles gained CSC structure which control the drug release at a lower rate. The multifunctional complex micelles were prepared for enhanced tumor therapy.     

Photo and redox dual-stimuli-responsive β-cyclodextrin-ferrocene supramolecules for drug delivery

Abstract

Amphiphilic photo and redox dual-stimuli-cleavable β-cyclodextrin-ferrocene supramolecules were synthesized through noncovalent interactions of ferrocene (Fc) and β-cyclodextrin (β-CD) born by 5-hydroxy-2-nitrobenzyl alcohol (ONB), a photodegradable linker between the β-CD and poly(4-substituted-?-caprolactone) (PXCL _n ) chain. The terminal host–guest MPEG-Fc/β-CD-ONB-PXCL _n complex can formed micelles in the aqueous phase. The critical micelle concentration ranged from 3.16 to 11.50?mg L^?1. The drug-loading content and drug entrapment efficiency of the complex were lower than those of the parent β-CD. When exposed to ultraviolet irradiation and hydrogen peroxide, complex micelles could dissociate and efficiently release the loaded drug. Nanoparticles exhibited almost no toxicity at concentrations up to 1000?μg mL^?1. The uptake of doxorubicin-incorporated micelles by HeLa cells was faster than that of free doxorubicin within the first 5?min. DOX-loaded MPEG₄₅-Fc/β-CD-ONB-PMCL₂₃ micelles effectively inhibited the proliferation of HeLa cells with a half maximal inhibitory concentration (IC₅₀) of 3.8?µg mL^?1.     

Matrix‐assisted laser desorption/ionization imaging mass spectrometry of oxaliplatin derivatives in heated intraoperative chemotherapy (HIPEC)‐like treated rat kidney

Oxaliplatin [1,2‐diaminocyclohexane (dach)‐Pt complex] is a platinum anticancer drug which is mainly used in the treatment of advanced colorectal cancer, particularly in Heated Intraoperative Chemotherapy (HIPEC) for the treatment of colorectal peritoneal carcinomatosis. In order to better understand the penetration of oxaliplatin in treated tissues we performed a direct imaging of tissue sections from HIPEC‐like treated rat kidney using matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry. This procedure allowed the detection and localization of oxaliplatin and its metabolites, the monocysteine and monomethionine complexes, in kidney sections. Specifically, oxaliplatin and its metabolites were localized exclusively in the kidney cortex, suggesting that it did not penetrate deeply into the organ. Based on these results, an imaging analysis of human tumors collected after HIPEC is currently in progress to assess the distribution of oxaliplatin and/or metabolites with the aim of defining clinical conditions to improve drug penetration. Copyright © 2010 John Wiley & Sons, Ltd.     

Formation and microstructure transition of F127/TX-100 complex

Formation and structure transition of the complex composed of triblock copolymer F127 and nonionic surfactant TX-100 have been investigated by 1H NMR spectroscopy, dynamic light scattering (DLS), and isothermal titration calorimetry (ITC). Three TX-100 concentration regions are identified, within which TX-100/20 mg/mL F127 complex undergoes different temperature-induced structure transitions. In low concentration region (< 9.42 mM), F127 single molecular species (unimers) wrap around TX-100 micelles forming F127/TX-100 complex with TX-100 micelle as the skeleton at a lower temperature (5 degrees C), and the skeleton transfers to F127 micelle at higher temperature (40 degrees C); in intermediate TX-100 concentration region (9.42-94.85 mM), the skeleton of F127/TX-100 complex transfers from TX-100 micelle successively into F127 micelle and TX-100 micelle again upon heating. The interaction of F127 with TX-100 is saturated in high TX-100 concentration region (> 157.57 mM), and free TX-100 micelles coexist with larger clusters of F127/TX-100 complexes. In addition, TX-100-induced F127/TX-100 complex formation and structure transition are also investigated at constant temperatures. The results show that within 5-10 degrees C, F127 unimers mainly adsorb on the surface of TX-100 micelles just like normal water soluble polymers; in the temperature region of 15-25 degrees C, TX-100 micelles prompts F127 micelle formation. Within 30-40 degrees C, TX-100 inserts into F127 micelles leading to the breakdown of F127 aggregates at higher TX-100 concentrations, and the obtained unimers thread through TX-100 micelles forming complex with TX-100 micelle as skeleton.     

Salt effect on the complex formation between polyelectrolyte and oppositely charged surfactant in aqueous solution

The complex formation between sodium carboxymethylcellulose (NaCMC) and dodecyltrimethylammonium bromide (DTAB) at various sodium bromide concentrations (C(NaBr)) has been studied by microcalorimetry, turbidimetric titration, steady-state fluorescence measurements, and the fluorescence polarization technique. The addition of salt is found to influence the formation of NaCMC/DTAB complexes markedly. At C(NaBr) = 0.00, 0.01, 0.02, 0.10, and 0.20 M, DTAB monomers form micelle-like aggregates on NaCMC chains to form NaCMC/DTAB complexes above the critical surfactant concentration (C1). At C(NaBr) = 0.23 M, DTAB molecules first form micelles above a 2.46 mM DTAB concentration prompted by the added salt, and then, above C1 = 4.40 mM, these micelles can aggregate with NaCMC chains to form NaCMC/DTAB complexes. However, at C(NaBr) = 0.25 M, there is no NaCMC/DTAB complex formation because of the complete salt screening of the electrostatic attraction between DTAB micelles and NaCMC chains. It is also surprisingly found that the addition of NaBr can bring out a decrease in C1 at C(NaBr) < 0.20 M. Moreover, the addition of NaBr to a mixture of 0.01 g/L NaCMC and 3.6 mM DTAB can directly induce the formation of NaCMC/DTAB complexes. This salt-enhancing effect on the complex formation is explained as the result of competition between the screening of interaction of polyelectrolyte with surfactant and the increasing of polyelectrolyte/surfactant interaction owing to the growth of micelles by added salt. When the increasing of polyelectrolyte/surfactant interaction exceeds the screening of interaction, the complex formation can be enhanced.     

Gold-labeled block copolymer micelles reveal gold aggregates at multiple subcellular sites

There is increasing interest in the usefulness of block copolymer micelles as drug delivery vehicles. However, their subcellular distribution has not been explored extensively, mostly because of the lack of adequately labeled block copolymers. In a previous study, we showed that fluorescently labeled block copolymer micelles entered living cells and co-localized with cytoplasmic organelles selectively labeled with fluorescent dyes. The details of the observed co-localizations were, however, limited by the resolution of the fluorescence approach, which is ca. 500 nm. Using transmission electron microscopy (TEM), we established time- and concentration-dependent subcellular distributions of gold-labeled micelles within human embryonic kidney (HEK 293) cells and human lung carcinoma (A549) cells. Gold particles were incorporated into poly(4-vinylpyridine)-block-poly(ethylene oxide) (P4VP21-b-PEO45) micelles. Data from dynamic light scattering (DLS) and TEM analyses revealed that the sizes of the gold particles ranged from 4 to 8 nm. The cells survived up to 24 h in the presence of low gold-labeled micelle concentrations (0.73 microg/mL), but cell death occurred at higher concentrations (i.e., kidney cells are more susceptible than lung cells). Over 24 h periods of equivalent exposure, lung cells internalized significantly more gold-incorporated micelles than kidney cells. Although micelles were added to the cell culture media as dispersed colloidal particles, the presence of serum in these media caused aggregation. These aggregates occurred mainly close to the cell plasma membrane at early times (5-10 min); however, at later times (24 h) aggregated particles were seen inside endosomes and lysozomes. Thus, gold-incorporated (labeled) micelles can serve as a valuable extension of the fluorescence approach to visualizing the localization of micelles in subcellular compartments, improving the resolution by at least 20-fold.     

Histology and antitumor activity study of PTX-loaded micelle,a fluorescent drug delivery system prepared by PEG-TPP

We synthesized PEG-TPP as carrier to encapsulate paclitaxel(PTX) in the form of micelles to overcome its water-solubility problem. PTX-loaded micelles possess a-week stability and appropriate particle size(152.1 ±1.2 nm) which is beneficial for enhanced permeability and retention(EPR) effect. Strong pH dependence of PTX releasing from micelles is verified by in vitro release study. At cellular level, PTXloaded micelles can target mitochondria effectively which may results a better cytotoxicity of micelles(especially IC50= 0.123 ± 0.035 mmol/L of micelles and 0.298 ± 0.067 mmol/L of PTX alone on MCF-7 cells). The fluorescence distributions of both isolated and sliced organs show that the micelles can effectively target tumors. Moreover, we further prove the enhanced therapeutic effects of micelles in tumor-bearing mice comparing with PTX alone. The results show that the biodegradable drug delivery system prepared by PEG-TPP can overcome the poor solubility of paclitaxel and improve its tumor targeting and antitumor activity.     

Synthesis and biological evaluation of new mono naphthalimide platinum(IV) derivatives as antitumor agents with dual DNA damage mechanism

Naphthalimide has emerged as an interesting DNA intercalator and possessed attracting antitumor properties. In this context, naphthalimide group was linked to platinum(IV) core to construct a series of new mono naphthalimide platinum(IV) derivatives. The title compounds exert effective antitumor activities to the tested tumor cells lines in vitro, especially the one with propionyl chain displays comparable or even better bioactivities than platinum(II) reference drugs cisplatin and oxaliplatin. Moreover, the mono naphthalimide platinum(IV) derivative displays comparable tumor growth inhibitory competence against CT26 xenograft tumors in BALB/c mice in vivo without severe toxic effects in contrast to oxaliplatin. A dual DNA damage mechanism was proven for the title complex. Both naphthalimide ligand and the liberated platinum(II) moiety could generate DNA lesions to tumor cells synergistically and active the apoptotic pathway by up-regulating the expression of caspase 9 and caspase 3. Meanwhile, the conversion of platinum(II) drug into tetravalent form by incorporating naphthalimide moiety increases the uptake of platinum in whole cells and DNA remarkably. All these facts might be the factors for the title platinum(IV) complexes to overcome platinum(II) drug resistance. Additionally, the mono naphthalimide platinum(IV) complex could interact with human serum albumin by hydrogen bond and van der Waals force which would further influence their storage, transport and bioactivities.     

键合紫杉醇的纳米胶束与C6胶质瘤细胞的相互作用

制备了键合紫杉醇(PTX)的聚乙二醇-聚乳酸嵌段共聚物(PEG-PLA/PTX)的纳米胶束, 采用四氮唑(MTT)比色法、流式细胞术、透射电镜及激光共聚焦显微镜等技术, 考察了PEG-PLA/PTX胶束对C6胶质瘤细胞的影响, 包括C6细胞超微结构的变化和细胞周期的改变, 以及纳米颗粒在细胞内的分布, 探讨了PEG-PLA/PTX胶束对肿瘤细胞的作用机理. 结果表明, PEG-PLA/PTX胶束进入到C6细胞内, 聚集于细胞浆中, 通过与细胞核中DNA的作用改变细胞生长的周期, 造成在G2-M期的阻滞, 引起细胞的凋亡. 因此, PEG-PLA/PTX胶束有望用于脑胶质瘤的化疗.     

Block ionomer complex micelles based on the self-assembly of poly(ethylene glycol)-block-poly(acrylic acid) and CdCl₂ for anti-tumor drug delivery

A novel block ionomer complex micelles as drug carrier is developed utilizing self-assemble of poly(ethylene glycol)-block-poly(acrylic acid) (PEG-b-PAA) and cadmium chloride. This micelles are characterized to be have good bio-compatibility, hydrophilicity, passive targeting and sustained slow release property which shows great potential for liver cancer therapy. Block ionomer complex micelles based on PEG-b-PAA and cadmium chloride can self-assemble in distilled water, and Cd(2+) agent is entrapped into the core stabilized by PEG shells. Results showed the block ionomer complex micelles to be spherically shaped. Cadmium was incorporated easily into the ionic core with remarkably high efficiency (34.25% weight (wt)/wt). The cadmium-loaded polymeric micelles exhibited sustained and slow release behavior of cadmium and a potent cytotoxicity against SMMC-7721 in vitro. This novel block ionomer complex micelles with cores of metal antitumor drug indicates to be potential carriers for effective drug delivery.     

The effect of block copolymer structure on the internalization of polymeric micelles by human breast cancer cells

The objective of this study was to assess the effect of hydrophilic/hydrophobic block chain lengths on the internalization of poly(ethylene oxide)-block-poly(varepsilon-caprolactone) (PEO-b-PCL) micelles by cancer cells. PEO-b-PCL block copolymers with varied PEO and PCL chain lengths were synthesized, assembled to polymeric micelles and loaded with a hydrophobic fluorescent probe (DiI) through a co-solvent evaporation method of physical encapsulation. The slow release of the fluorescent probe from the micellar structure was evidenced following DiI transfer to lipid vesicles. The extent of micellar uptake by cancer cells was investigated through their incubation with MCF-7 cells followed by measurement of the fluorescent emission intensity of DiI (lambda=550 nm) in separated lysed cells. Cellular internalization of polymeric micelles was confirmed by laser scanning microscopy. The mechanism of micellar uptake was investigated by pretreatment of MCF-7 cells with chlorpromazine and cytochalasin B. Encapsulation of DiI in PEO-b-PCL micelles lowered the extent and rate of hydrophobic probe internalization by cancer cells. For polymeric micelles with 5000 gmol(-1) of PCL and varied PEO molecular weights of 2000, 5000 and 13,000 gmol(-1), maximum uptake was observed at a PEO molecular weight of 5000 gmol(-1). For polymeric micelles with 5000 gmol(-1) of PEO and varied PCL molecular weights of 5000, 13,000 and 24,000 gmol(-1), maximum uptake was observed at 13,000 gmol(-1) of PCL. Chlorpromazine reduced the cellular uptake of PEO-b-PCL micelles independent from the block copolymer structure, pointing to the involvement of clathrin mediated endocytosis mechanisms in the uptake of polymeric micelles by cancer cells. Inhibition of cellular uptake of PEO-b-PCL micelles by cytochalasin B, on the other hand, was found to be dependent on the chemical structure of the core/shell forming blocks.     

Photoinduced electron transfer from N,N-dimethylaniline to 7-amino coumarins in protein-surfactant complex: slowing down of electron transfer dynamics compared to micelles

Photoinduced electron transfer from N,N-dimethylaniline to different Coumarin dyes has been investigated in dodecyl trimethyl ammonium bromide (DTAB) micelles and in Bovine serum albumin (BSA)-DTAB protein-surfactant complex using steady-state and picosecond time-resolved fluorescence spectroscopy. We observed a slower fluorescence quenching rate in the DTAB micelles and in the protein-surfactant complex as compared to that in pure acetonitrile solution. Moreover, the observed fluorescence quenching in BSA-DTAB complex was found to be slower than that in DTAB micelles. In the correlation of free-energy change with the fluorescence quenching constant we observed a deviation in the fluorescence quenching electron transfer rate for Coumarin 151 (C-151) from the normal Marcus curve. This observation is ascribed to the stronger interaction of C-151 with the surfactant molecules present in the micelles. This is evident from the slower translation diffusion (D(L)) of Coumarin 151 compared to other probe molecules.     

Lactosylated poly(ethylene glycol)-siRNA conjugate through acid-labile beta-thiopropionate linkage to construct pH-sensitive polyion complex micelles achieving enhanced gene silencing in hepatoma cells

The remarkably enhanced gene silencing in hepatoma cells was achieved by assembling lactosylated-PEG-siRNA conjugates bearing acid-labile beta-thiopropionate linkages into polyion complex (PIC) micelles through the mixing with poly(l-lysine). The PIC micelles with clustered lactose moieties on the periphery were successfully transported into hepatoma cells in a receptor-mediated manner, releasing hundreds of active siRNA molecules into the cellular interior responding to the pH decrease in the endosomal compartment. Eventually, almost 100 times enhancement in gene silencing activity compared to that of the free conjugate was achieved for the micelle system, facilitating the practical utility of siRNA therapeutics.     

Study on Synergistic Effect Between Wormlike Micelles and Hydrophobically Modified Poly(acrylic acid) in Salt Solution

The complex system of hydrophobically modified poly (acrylic acid) (HMPA) and wormlike micelles formed by sodium oleate in the presence of sodium acetate is investigated by apparent viscosity and rheological measurements. Addition of small amount of HMPA markedly enhances the viscosity of wormlike micelles, with further increase of HMPA concentration, a viscosity drop is observed. At high salinity, the complex system still remains strong viscoelastic and eliminates the limitation of susceptibility to salt for HMPA. DPD simulation results are in good agreement with experimental data, which provide theoretical confirmation for a synergistic mechanism between HMPA and wormlike micelles.