Dissipative particle dynamics simulation of gold nanoparticles stabilization by PEO–PPO–PEO block copolymer micelles

Dissipative particle dynamics (DPD) was used to simulate the formation and stabilization of gold nanoparticles in poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (PEO–PPO–PEO) block copolymer micelles. Primary gold clusters that were experimentally observed in the early stage of gold nanoparticle formation were modeled as gold bead in DPD simulation. It showed that gold beads were wrapped by the block copolymer and aggregated into spherical particles inside the micelles and forming stable Pluronic–gold colloids with two-layer structures. Increasing Pluronic concentration, molecular weight, and PPO block length led to the formation of more uniform and more stable gold nanoparticles. Density profiles of water beads suggested that the micelles, especially the hydrophobicity of the micellar cores, played an important role in stabilizing gold nanoparticles. Dynamic process indicated that the formation of gold nanoparticles was controlled by the competition between aggregation of primary gold clusters and the stabilization by micelles of block copolymers.. The DPD simulation results of gold–copolymer–water system agree well with previous experiments, while more structure information on microscopic level could be provided.     

Mechanism of gold metal ion reduction, nanoparticle growth and size control in aqueous amphiphilic block copolymer solutions at ambient conditions

Spontaneous formation and efficient stabilization of gold nanoparticles with an average diameter of 7 approximately 20 nm from hydrogen tetrachloroaureate(III) hydrate (HAuCl4.3H2O) were achieved in air-saturated aqueous poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymer solutions at ambient temperature in the absence of any other reducing agent. The particle formation mechanism is considered here on the basis of the block copolymer concentration dependence of absorption spectra, the time dependence (kinetics) of AuCl4- reduction, and the block copolymer concentration dependence of particle size. The effects of block copolymer characteristics such as molecular weight (MW), PEO block length, PPO block length, and critical micelle concentration (cmc) are explored by examining several PEO-PPO-PEO block copolymers. Our observations suggest that the formation of gold nanoparticles from AuCl4- comprises three main steps: (1) reduction of metal ions by block copolymer in solution, (2) absorption of block copolymer on gold clusters and reduction of metal ions on the surface of these gold clusters, and (3) growth of metal particles stabilized by block copolymers. While both PEO and PPO blocks contribute to the AuCl4- reduction (step 1), the PEO contribution appears to be dominant. In step 2, the adsorption of block copolymers on the surface of gold clusters takes place because of the amphiphilic character of the block copolymer (hydrophobicity of PPO). The much higher efficiency of particle formation attained in the PEO-PPO-PEO block copolymer systems as compared to PEO homopolymer systems can be attributed to the adsorption and growth processes (steps 2 and 3) facilitated by the block copolymers. The size of the gold nanoparticles produced is dictated by the above mechanism; the size increases with increasing reaction activity induced by the block copolymer overall molecular weight and is limited by adsorption due to the amphiphilic character of the block copolymers.     

Spontaneous formation of gold nanoparticles in poly(ethylene oxide)-poly(propylene oxide) solutions: solvent quality and polymer structure effects

We report here on the effects that the solution properties of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymers have on the reduction of hydrogen tetrachloroaurate(III) hydrate (HAuCl4.3H2O) and the size of gold nanoparticles produced. The amphiphilic block copolymer solution properties were modulated by varying the temperature and solvent quality (water, formamide, and their mixtures). We identified two main factors, (i) block copolymer conformation or structure (e.g., loops vs entanglements, nonassociated polymers vs micelles) and (ii) interactions between AuCl4- ions and block copolymers (attractive ion-dipole interactions vs repulsive interactions due to hydrophobicity), to be important for controlling the competition between the reactivities of AuCl4- reduction in the bulk solution to form gold seeds and on the surface of gold seeds (particles) and the particle size determination. The particle size increase observed with increased temperature in aqueous solutions is attributed to enhanced hydrophobicity of the block copolymer, which favors AuCl4- reduction on the surface of seeds. The lower reactivity and higher particle sizes observed in formamide solutions are attributed to the shielding of ion-dipole interaction between AuCl4- ions and block copolymers by formamide, which overcomes the beneficial effects of formamide on the block copolymer conformation (lower micelle concentration).     

Single-step synthesis and stabilization of metal nanoparticles in aqueous pluronic block copolymer solutions at ambient temperature

A single-step synthesis of gold nanoparticles with an average diameter of approximately 10 nm from hydrogen tetrachloroaureate(III) hydrate (HAuCl4.3H2O) has been achieved in air-saturated aqueous solutions that contain poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymers but not any other reducing agent. These amphiphilic block copolymers act as both reductants and colloidal stabilizers and prove very efficient in both functions. The formation of gold nanoparticles is controlled by the overall molecular weight and relative block length of the block copolymer. The synthesis procedure reported here is environmentally benign and economic, as it involves the minimum possible number of components: it uses water as the solvent, it uses commercially available polymers, it proceeds fast to completion, and it results in a "ready-to-use" product.     

Temperature-responsive magnetite/PEO-PPO-PEO block copolymer nanoparticles for controlled drug targeting delivery

In this study, temperature-responsive magnetite/polymer nanoparticles were developed from iron oxide nanoparticles and poly(ethyleneimine)-modified poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymer. The particles were characterized by TEM, XRD, DLS, VSM, FTIR, and TGA. A typical product has an approximately 20 nm magnetite core and an approximately 40 nm hydrodynamic diameter with a narrow size distribution and is superparamagnetic with large saturation magnetization (51.34 emu/g) at room temperature. The most attractive feature of the nanoparticles is their temperature-responsive volume-transition property. DLS results indicated that their average hydrodynamic diameter underwent a sharp decrease from 45 to 25 nm while evaluating the temperature from 20 to 35 degrees C. The temperature-dependent evolution of the C-O stretching band in the FTIR spectra of the aqueous nanoparticles solution revealed that thermo-induced self-assembly of the immobilized block copolymers occurred on the magnetite solid surfaces, which is accompanied by a conformational change from a fully extended state to a highly coiled state of the copolymer. Consequently, the copolymer shell could act as a temperature-controlled "gate" for the transit of guest substance. The uptake and release of both hydrophobic and hydrophilic model drugs were well controlled by switching the transient opening and closing of the polymer shell at different temperatures. A sustained release of about 3 days was achieved in simulated human body conditions. In primary mouse experiments, drug-entrapped magnetic nanoparticles showed good biocompatibility and effective therapy for spinal cord damage. Such intelligent magnetic nanoparticles are attractive candidates for widespread biomedical applications, particularly in controlled drug-targeting delivery.     

Amphiphilic polymers as pseudotemplates in the synthesis of metal sols

The effects of poly(ethylene glycol) and its amphiphilic polymers on the products of copper ion reduction in aqueous solutions are studied. Whereas coarse metal dispersions are formed in poly(ethylene glycol) solutions, stable sols of metal nanoparticles with diameters of 2 nm and above are produced in the presence of poly(ethylene glycol monolaurate) and poly(ethylene glycol monostearate). A poly(ethylene glycol)-poly(propylene glycol) block copolymer (Pluronic) also stabilizes copper nanoparticles; however, the interaction product of this copolymer with nanoparticles forms a precipitate. According to the electron microscopy data, sol particles comprise polymer micelles containing included copper nanoparticles.     

Poly(ethylene oxide)-poly(styrene oxide)-poly(ethylene oxide) copolymers: Micellization, drug solubilization, and gelling features

Two new poly(ethylene oxide)-poly(styrene oxide) triblock copolymers (PEO-PSO-PEO) with optimized block lengths selected on the basis of previous studies were synthesized with the aim of achieving a maximal solubilization ability and a suitable sustained release, while keeping very low material expense and excellent aqueous copolymer solubility. The self-assembling and gelling properties of these copolymers were characterized by means of light scattering, fluorescence spectroscopy, transmission electron microscopy, and rheometry. Both copolymers formed spherical micelles (12-14 nm) at very low concentrations. At larger concentration (>25 wt%), copolymer solutions showed a rich phase behavior, with the appearance of two types of rheologically active (more viscous) fluids and of physical gels depending on solution temperature and concentration. The copolymer behaved notably different despite their relatively similar block lengths. The ability of the polymeric micellar solutions to solubilize the antifungal drug griseofulvin was evaluated and compared to that reported for other structurally-related block copolymers. Drug solubilization values up to 55 mg g⁻¹ were achieved, which are greater than those obtained by previously analyzed poly(ethylene oxide)-poly(styrene oxide), poly(ethylene oxide)-poly(butylene oxide), and poly(ethylene oxide)-poly(propylene oxide) block copolymers. The results indicate that the selected SO/EO ratio and copolymer block lengths were optimal for simultaneously achieving low critical micelle concentrations (cmc) values and large drug encapsulation ability. The amount of drug released from the polymeric micelles was larger at pH 7.4 than at acidic conditions, although still sustained over 1 day.     

Monolayer-protected gold nanoparticles by the self-assembly of micellar poly(ethylene oxide)-b-poly(epsilon-caprolactone) block copolymer

A study is presented of the preparation of gold nanoparticles incorporated into biodegradable micelles. Poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-b-PCL) copolymer was synthesized by ring-opening polymerization, and the hydroxyl end group of the PCL block was modified with thioctic acid using dicyclohexyl carbodiimide as the coupling reagent. The PEO-b-PCL-thioctate ester (TE) thus obtained was used in a later step to form monolayer protected gold nanoparticles via the thioctate spacer. Gold nanoparticles stabilized with the PEO-b-PCL block (named Au/Block (x/y), where x/y is the mole feed ratio between HAuCl4 and PEO-b-PCL-TE) were prepared and analyzed. Au/Block (1/1), Au/Block (2/1), and Au/Block (3/1) nanoparticles were found to form stable dispersions in the organic solvents commonly used to dissolve the unlabeled block copolymer. The average diameter of the nanoparticles was determined by transmission electron microscopy (TEM) and found to be 6+/-2 nm. Au/Block (4/1) nanoparticle dispersions in organic solvents, on the other hand, were not stable and produced large gold clusters (50-100 nm). Cluster formation was attributed to the low grafting density of the block copolymer, which facilitates agglomeration. For Au/Block (12/1), along the same trend, only an insoluble product was isolated. Micelles in water were prepared by the slow addition of the dilute Au/Block solution in dimethylformamide into a large excess of water with vigorous stirring. Au/Block (1/1) and Au/Block (2/1) formed nanosized structures of 5-7 nm. TEM images of stained Au/Block (1/1) micelles, made in water, clearly showed the formation of core-shell structures. Au/Block (3/1) micelles, on the other hand, were not stable and large agglomerates a few microns in size were observed. The study focuses on the synthesis, characterization, and aggregation behavior of gold-loaded PEO-b-PCL block copolymer micelles, a potential system for drug delivery in conjunction with tissue and subcellular localization studies.     

Preparation of stable gold nanoparticles by using diblock copolymer mixture as encapsulating agent

Gold nanoparticles by using the mixture of polystyrene-block-poly(2-vinyl pyridine)/poly(2-vinyl pyridine)-block-poly(ethylene oxide) (PS-b-P2VP/P2VP-b-PEO) block copolymers as encapsulating agent was prepared. The prepared nanoparticles were characterized by transmission electron microscopy, UV-Vis spectroscopy and contact angle. It is demonstrated that the obtained gold nanoparticles are covered with mixed block copolymer shells. The hydrophilic property of the nanoparticles can be varied by the change of the dispersion medium. The obtained gold nanoparticles with mixed block copolymer shells are stable in organic solvents (such as tetrahydrofuran and toluene) and water.     

Microenvironment in the corona region of triblock copolymer micelles: temperature dependent solvation and rotational relaxation dynamics of coumarin dyes

Dynamic Stokes' shift and fluorescence anisotropy measurements using coumarin-153 (C153) and coumarin-151 (C151) as the fluorescence probes have been carried out in aqueous poly(ethylene oxide)20-poly(propylene oxide)70-poly(ethylene oxide)20 (P123) and poly(ethylene oxide)100-poly(propylene oxide)70-poly(ethylene oxide)100 (F127) block copolymer micelles with an aim to understand the water structures and dynamics in the micellar corona region. It has been established that the probes reside in the micellar corona region. It is indicated that the corona regions of P123 and F127 micelles are relatively less hydrated than the Palisade layers of neutral micelles like Triton-X-100 and Brij-35. From the appraisal of total Stokes' shift values for the probes in the two block copolymer micelles, it is inferred that the F127 micelle is more hydrated than the P123 micelle. It is observed that the dynamic Stokes' shift values for both of the probes remain more or less similar at all the temperatures studied in the P123 micelle. For C153 in F127, however, the observed Stokes' shift is seen to decrease quite sharply with temperature, though it remains quite similar for C151. Moreover, the fraction of the unobserved initial dynamic Stokes' shift is appreciably higher for both the probes in the F127 micelle compared to that in P123. Over the studied temperature range of 293-313 K, the spectral shift correlation function is described adequately by a bi-exponential function. Rotational relaxation times for C153 in both the micelles show a kind of transition at around 303 K. These results have been rationalized assuming collapse of the poly(ethylene oxide) (PEO) blocks and formation of water clusters in the corona region due to dehydration of poly(ethylene oxide) blocks with an increase in temperature. A dissimilar probe location has been inferred for the differences in the results with C153 and C151 probes in F127. Comparison of the microviscosity and the hydration of the block copolymer micelles has also been made with those of the other commonly used neutral micelles, for a better understanding of the results in the block copolymer micelles.     

Dynamic and static light scattering studies on self-aggregation behavior of biodegradable amphiphilic poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene oxide) triblock copolymers in aqueous solution

The self-aggregation behavior of two amphiphilic poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene oxide) (PEO-PHB-PEO) triblock copolymer samples with nearly identical PHB block lengths but different PEO block lengths, PEO-PHB-PEO(2000-810-2000) and PEO-PHB-PEO(5000-780-5000), was studied with dynamic and static light scattering (DLS and SLS), in combination with fluorescence spectroscopy and transmission electron microscopy (TEM). The formation of polymeric micelles by the two PEO-PHB-PEO triblock copolymers was confirmed with fluorescence technique and TEM. DLS analysis showed that the hydrodynamic radius (R(h)) of the monodistributed polymeric micelles increased with an increase in PEO block length. The relative thermostability of the triblock copolymer micelles was studied by SLS and DLS at different temperatures. The aggregation number and the ratio of the radius of gyration over hydrodynamic radius were found to be independent of temperature, probably due to the strong hydrophobicity of the PHB block. The combination of DLS and SLS studies indicated that the polymeric micelles were composed of a densely packed core of hydrophobic PHB blocks and a corona shell formed by hydrophilic PEO blocks. The aggregation numbers were found to be approximately 53 for PEO-PHB-PEO(2000-810-2000) micelles and approximately 37 for PEO-PHB-PEO(5000-780-5000) micelles. The morphology of PEO-PHB-PEO spherical micelles determined by DLS and SLS measurements was further confirmed by TEM.     

Preparation of gold microparticles using halide ions in bulk block copolymer phases via photoreduction

Gold microparticles were prepared from the gold salt in the solid bulk phase of a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymer via a photoreduction process in the presence of halide ions. The shapes and sizes of the gold microparticles were found to be dependent on the types and amount of halide ions as well as the types of cations used due to the combined effects of the adsorption power and oxidative dissolution ability of the additives on gold surfaces. Gold nanorods were obtained when poly(ethylene oxide) was used instead of the block copolymer. This suggests that the poly(propylene oxide) (PPO) parts in the block copolymer are essential for the formation of gold microparticles, even though the degree of the direct interaction between the PPO blocks and gold salt is not significant.     

PEO-PPO-PEO水溶液体系胶束化及凝胶化行为的耗散粒子动力学模拟

采用耗散粒子动力学(Dissipative particle dynamics, DPD)模拟方法研究了三嵌段共聚物聚氧乙烯-聚氧丙烯-聚氧乙烯(PEO-PPO-PEO)的胶束化和凝胶化行为. 通过模拟得到了F127(EO₉₉PO₆₅EO₉₉)水溶液的临界胶束浓度和临界凝胶浓度. 结果发现, 在298 K、 质量分数低于40%时, F127水溶液中形成的胶束形状均为球形. 此外,进一步研究了亲水嵌段长度对胶束结构及凝胶形成浓度的影响, 结果发现, 亲水嵌段越短, 越有利于长椭球状胶束的形成, 而临界凝胶浓度随着亲水嵌段PEO长度的增加而降低.     

Formation of gold@polymer core-shell particles and gold particle clusters on a template of thermoresponsive and pH-responsive coordination triblock copolymer

Template synthesis of various morphological gold colloidal nanoparticles using a thermoresponsive and pH-responsive coordination triblock copolymer of poly(ethylene glycol)-b-poly(4-vinylpyridine)-b-poly(N-isopropylacrylamide) is studied. The template morphology of the thermoresponsive and pH-responsive coordination triblock copolymer, which can be tuned by simply changing the pH or temperature of the triblock copolymer aqueous solution, ranges from single chains to core-corona micelles and further to micellar clusters. Various morphological gold colloidal nanoparticles such as discrete gold nanoparticles, gold@polymer core-shell nanoparticles, and gold nanoparticle clusters are synthesized on the corresponding template of the triblock copolymer by first coordination with gold ions and then reduction by NaBH4. All three resultant gold colloidal nanoparticles are stable in aqueous solution, and their sizes are 2, 10, and 7 nm, respectively. The gold@polymer core-shell nanoparticles are thermoresponsive. The gold nanoparticle cluster has a novel structure, and each one holds about 40 single gold nanoparticles.     

Amphiphilic ABC triblock copolymer-assisted synthesis of core/shell structured CdTe nanowires

A new type of amphiphilic ABC triblock copolymer, poly(acrylic acid)(33)-poly(styrene)(47)-poly(ethylene oxide)(113) (PAA(33)-PS(47)-PEO(113)), was designed to assist the synthesis of core/shell structured CdTe nanowires via a one-step synthetic route. The PAA block was adopted to capture cadmium ions as the precursor of CdTe. Due to the bivalent coordination of Cd(2+), the copolymer in dioxane/H(2)O formed micelles with Cd(2+)-polychelate cores. Then CdTe nanocrystals were obtained within the micelles after introduction of NaHTe into the micelle solution. Transmission electron microscopy experiments revealed that the CdTe nanocrystals obtained simultaneously formed "pearl-necklace" aggregates in solution possibly driven by dipole interactions between neighboring particles, and then single crystalline CdTe nanowires upon reflux. Accompanying this morphology change, a phase transition from cubic zinc blende to wurtzite structure was observed by selected-area electron diffraction. The aggregation of the PS block in dioxane with a certain amount of H(2)O enabled the PS blocks to form a densely packed shell on the CdTe nanowires whose typical size is 700-800 nm in length and 15-20 nm in width. The third block of PEO was employed to render the finally formed CdTe nanowires dispersibility.     

Probing paeonol-pluronic polymer interactions by 1H NMR spectroscopy

By using a combination of 1H NMR spectroscopy, two-dimensional heteronuclear single-quantum coherence-resolved (1)H{(13)C} and homonuclear rotating-frame Overhauser enhancement NMR correlation experiments with diffusion ordered spectroscopy (DOSY), the location and distribution of a hydrophobic drug, paeonol, have been established with respect to the methyl groups of the poly(ethylene oxide)-poly(propylene oxide) -poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymer. The interaction between them is adjustable according to the different temperature-dependent hydrophilicities or hydrophobicities of the triblock copolymer components. On the other hand, such interactions influence the self-assembly properties of the block copolymer amphiphiles in solution. The amount of anhydrous methyl groups of PPO segments shows an increase with increasing paeonol concentration. It was also demonstrated that the shell-crosslinking of the Pluronic polymer has an effect in increasing the amount of anhydrous methyl groups and thus increasing the hydrophobicity of Pluronic micelles. This might be the deeper reason underlying the increase in drug-loading capacity and prolongation in release time of Pluronic micelles for drug delivery after the shell-crosslinking. Changes in self-diffusion coefficients of paeonol with varying copolymer concentrations and types were also determined by the diffusion-based NMR DOSY technique, and values of K(a), DeltaG, and n were calculated.     

Block copolymer-mediated synthesis of size-tunable gold nanospheres and nanoplates

We have successfully controlled the size and shape of isotropic and anisotropic gold nanocrystals through a one-step reaction by using amphiphilic polyethylene oxide-polystyrene oxide block copolymers as both reductant and stabilizing agents in water solution. Spherical or quasispherical nanoparticles were obtained at room temperature with tunable mean sizes and polydispersities depending on reaction conditions, that is, on copolymer block length, and copolymer and gold salt concentrations. By moderate increases of reaction temperature up to 65 degrees C, progressive formation of single-crystalline gold nanoplates in good yields takes place (up to 70%) without the necessity of additional reactants or growing solutions. These nanoplates are characterized by lateral mean sizes between 0.1-1.2 microm depending on copolymer concentration and reaction temperature, with mainly truncated or rounded triangular shapes with {111} planes as two basal surfaces. This allows us to tune the surface plasmon band of the nanoplates from ca. 850 nm to more than 1100 nm, well inside the near-infrared region (NIR), which enables the use of these type of nanostructures as a very promsing materials in applications such as optical coatings, SERS, and cancer cell hyperthermia. We proposed that the growth of these nanostructures can stem from a decrease in the reaction rate as temperature increases due to an enhanced copolymer hydrophobicity, which gives rise to a structure of interacting micelles formed from the fluid via a percolation transition (known as "soft gel") at elevated temperatures. In this way, reduction becomes slow enough to allow kinetic control of the reaction, and preferential adsorption of the copolymer molecules/micelles on certain crystallographic planes can favor the growth of certain nanocrystal facets to give the final structure. This alternative water-based system provides a more convenient and environmentally benign route to the synthesis of shape-controlled noble-metal nanocrystals in high yield because it does not involve toxic organic solvents or reagents and serves as a bridge between two frontline discipline: the block copolymeric science and anisotropic nanoparticles.     

Syntheses of amphiphilic biodegradable copolymers of poly(ethyl ethylene phosphate) and poly(3-hydroxybutyrate) for drug delivery

Biodegradable and amphiphilic triblock copolymers poly(ethyl ethylene phosphate)-poly(3-hydroxy-butyrate)-poly(ethyl ethylene phosphate) (PEEP-b-PHB-b-PEEP) have been successfully synthesized through ring-opening polymerization. The structures are confirmed by gel permeation chromatography and NMR analyses. Crystallization investigated by X-ray diffraction reveals that the block copolymer with higher content of poly(ethyl ethylene phosphate) (PEEP) is more amorphous, showing decreased crystallizability. The obtained copolymers self-assemble into biodegradable nanoparticles with a core-shell micellar structure in aqueous solution, verified by the probe-based fluorescence measurements and transmission electronic microscopy (TEM) observation. The hydrophobic poly(3-hydroxybutyrate) (PHB) block serves as the core of the micelles and the micelles are stabilized by the hydrophilic PEEP block. The size and size distribution are related to the compositions of the copolymers. Paclitaxel (PTX) has been encapsulated into the micelles as a model drug and a sustained drug release from the micelles is observed. MTT assay also demonstrates that the block copolymers are biocompatible, rendering these copolymers attractive for drug delivery. Supported by the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No.20060358036)     

Synthesis and aqueous solution properties of functionalized and thermoresponsive poly(D,L-lactide)/polyether block copolymers

Tri- and pentablock amphiphilic copolymers containing hydrophobic poly(D,L-lactide) block(s) and hydrophilic polyethers were synthesized in order to obtain new precursor architectures suitable for drug delivery systems. Polyglycidol-6-poly(ethylene oxide)-b-poly(D,L-lactide) possess high hydroxyl functionality provided by the linear polyglycidol block. Thus very stable hydroxyl functionalized micelles in aqueous media were obtained. On the other hand poly(D,L-lactide)-b-poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide)-b-poly(D,L-lactide) form temperature sensitive aggregates. The copolymers obtained were analyzed by SEC and NMR, and their aqueous solution properties were followed by cloud point measurements and determination of critical micellization temperature. TEM was used for particles visualization.     

Iron hydroxide nanoparticles coated with poly(ethylene glycol)-poly(aspartic acid) block copolymer as novel magnetic resonance contrast agents for in vivo cancer imaging

PEG-coated β-FeOOH nanoparticles were prepared through electrostatic complex formation of iron oxide nanoparticles with poly(ethylene glycol)-poly(aspartic acid) block copolymer [PEG-P(Asp)] in distilled water. By dynamic light scattering (DLS) measurement, the nanopaticle size was determined to be 70 nm with narrow distribution. The FT-IR and zeta potential experimental results proved that PEG-PAsp molecules bound to the surface of the iron oxide nanoparticles via the coordination between the carboxylic acid residues in the PAsp segment of the block copolymer and the surface Fe of the β-FeOOH nanoparticles. The PEG-coated nanoparticles revealed excellent solubility and stability in aqueous solution as well as in physiological saline. In vivo MRI experiments on tumor-bearing mice demonstrated that the PEG-coated nanoparticles prepared by the current approach achieved an appreciable accumulation into solid tumor, suggesting their potential utility as tumor-selective MRI contrast agents.