Letters

Controlled Stacking of Charged Block Copolymer Micelles

Zhibin Li,†,§ Zhiyun Chen,‡ Honggang Cui,† Kelly Hales,† Karen L. Wooley,*,‡ andDarrin J. Pochan*,†

Materials Science and Engineering and Delaware Biotechnology Institute, UniVersity of Delaware,Newark, Delaware 19716, and Center for Materials InnoVation and Department of Chemistry,

Washington UniVersity in Saint Louis, Saint Louis, Missouri 63130

ReceiVed NoVember 10, 2006. In Final Form: January 19, 2007

Using poly(acrylic acid)-b-poly(methyl acrylate)-b-polystyrene (PAA-b-PMA-b-PS) triblock copolymers or a mixtureof different molecular weight PAA-b-PS diblock copolymers, stacks of polymeric micellar assemblies, such as disksand Y-shaped cylinders, were formed through intermicellar interactions. Whereas micelles hierarchically stackedtogether, micellar interactions within the stack defined a uniform micelle geometry and size for up to micrometersin length. The kinetic pathway dependence and stability of the stacked assemblies were studied, and possible intermicellarinteractions between micelles within the stacks are proposed.

Nanoscale phase separation of block copolymers in bulk andthin film systems has been used to form bulk functional materialsand patterned surfaces.1-6 Amphiphilic block copolymers thatassemble into polymer micelles have also been studied fornanotechnology applications7-12and drug-delivery systems.13-18

In this letter, stacks of polymer micellar assemblies, such as

disks, cylinders, and Y-shaped cylinders (Ys), are reported, whichform from amphiphilic linear block copolymers in tetrahydrofuran(THF)/water solvent mixtures. These well-arranged, stackedmicelle structures form in solution compositions that exist betweenthose that produce regions of bulk phase separation versus thosethat produce a discrete micellization of block copolymers. Figure1 shows micro- and nanoscale image examples of bulk phaseseparation, stacked micelles, and separated/discrete micelles. Theblock copolymer bulk phase separation forms a lamellarprecipitate, stacks of disks exist in an optically cloudy solutionwithout precipitation, and the solution of discrete micelles is

* Corresponding authors. E-mail: pochan@udel.edu, klwooley@artsci.wustl.edu.

† University of Delaware.‡ Washington University in Saint Louis.§ Present address: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield,

Connecticut 06877.(1) Whitesides, G. M.Small2005, 1, 172-179.(2) Russell, T. P.Curr. Opin. Colloid Interface Sci.1996, 1, 107-115.(3) Granick, S.; Kumar, S. K.; Amis, E. J.; Antonietti, M.; Balazs, A. C.;

Chakraborty, A. K.; Grest, G. S.; Hawker, C.; Janmey, P.; Kramer, E. J.; Nuzzo,R.; Russell, T. P.; Safinya, C. R.J. Polym. Sci., Part B: Polym. Phys.2003, 41,2755-2793.

(4) Fasolka, M. J.; Mayes, A. M.Annu. ReV. Mater. Res.2001, 31, 323-355.(5) Bates, F. S.Science1991, 251, 898-905.(6) Yan, X.; Liu, G.; Li, Z. J. Am. Chem. Soc.2004, 126, 10059-10066.(7) Vriezema, D. M.; Aragones, M. C.; Elemans, J. A. A. W.; Cornelissen,

J. J. L. M.; Rowan, A. E.; Nolte, R. J. M.Chem. ReV. 2005, 105, 1445-1489.(8) Behera, D. K.; Bag, D. S.; Alam, S.; Mathur, G. N.J. Polym. Mater.2004,

21, 81-88.(9) Wooley, K. L. J. Polym. Sci., Part A: Polym. Chem.2000, 38, 1397-

1407.(10) Foerster, S.; Antonietti, M.AdV. Mater. 1998, 10, 195-217.

(11) Moffitt, M.; Zhang, L.; Khougaz, K.; Eisenberg, G. A.NATO ASI Ser.,Ser. E1996, 327, 53-72.

(12) Zhang, L.; Eisenberg, A.Science1995, 268, 1728-1731.(13) Gaucher, G.; Dufresne, M.-H.; Sant, V. P.; Kang, N.; Maysinger, D.;

Leroux, J.-C.J. Controlled Release2005, 109, 169-188.(14) Le Garrec, D.; Ranger, M.; Leroux, J.-C.Am. J. Drug DeliVery 2004, 2,

15-42.(15) Nishiyama, N.; Bae, Y.; Miyata, K.; Fukushima, S.; Kataoka, K.Drug

DiscoVery Today: Technol.2005, 2, 21-26.(16) Vasir, J. K.; Reddy, M. K.; Labhasetwar, V. D.Curr. Nanosci.2005, 1,

47-64.(17) Otsuka, H.; Nagasaki, Y.; Kataoka, K.AdV. Drug DeliVery ReV. 2003,

55, 403-419.(18) Adams Monica, L.; Lavasanifar, A.; Kwon Glen, S.J. Pharm. Sci.2003,

92, 1343-1355.

© Copyright 2007American Chemical Society

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10.1021/la063292b CCC: $37.00 © 2007 American Chemical SocietyPublished on Web 03/31/2007

translucent. All of the stacked structures reported here were stablein solution for at least several weeks. The stacks of disks observedwere kinetic pathway-independent and could be formed startingfrom the micellar region or phase-separated region. These stackedstructures may make it possible to fabricate novel alternatingfunctional materials and may also be used to generate uniquepolymeric micelles that are uniform in size and morphology butare otherwise difficult to obtain, such as Y-shaped cylinders oruniform disks.

In previous studies, different polymer micellar structures,formed from poly(acrylic acid)-b-poly(methyl acrylate)-b-polystyrene (PAA-b-PMA-b-PS) triblock copolymers in THF/water mixtures with diamine as the counterion, were reported,

including toroids,19,20disks,21 cylinders, and spheres.21 Both thetype and amount of diamine were found to be important indetermining the specific micellar morphology. Different diaminecounterions, THF/water ratios, and block copolymer architectureshave also been used to probe and control the micellar structure.It was found in the most recent studies that stacked assembliesof several of the morphologies, including disks, cylinders, andYs, could be constructed using similar strategies. The stacks

(19) Pochan, D. J.; Chen, Z.; Cui, H.; Hales, K.; Qi, K.; Wooley, K. L.Science2004, 306, 94-97.

(20) Chen, Z.; Cui, H.; Hales, K.; Li, Z.; Qi, K.; Pochan, D. J.; Wooley, K.L. J. Am. Chem. Soc.2005, 127, 8592-8593.

(21) Li, Z.; Chen, Z.; Cui, H.; Hales, K.; Qi, K.; Wooley, K. L.; Pochan, D.J. Langmuir2005, 21, 7533-7539.

Figure 1. Phase behavior for S203 triblock copolymers in THF/water solvent mixtures with the addition of EDDA diamine in a 1:1 amine/acidratio. (Top) At low water content (<30%), the block copolymer phase separates to form lamellar precipitate globules. At high water content,individual disks were formed (translucent). Stacks of disks (very cloudy solutions without precipitate) can be obtained at intermediate solutionconditions. (Bottom) TEM micrographs of phase separation (left), stack of disks formed at 40% water (middle), and discrete disks togetherwith spherical micelles (right). The stacks can be micrometers in length. TEM micrographs of discrete disks have been reported.21 Colors(red, blue, and brown) in the cartoons correspond to PS, PMA, and PAA blocks, respectively.

Chart 1. Block Copolymers Used to Form Stacks

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represent a unique hierarchical assembly that can grow up toseveral micrometers in length through long-range intermicellarelectrostatic interactions along the stacking axis. At the sametime, the stacking building blocks, the fundamental nanoscopicmicellar assemblies of the amphiphilic polyelectrolyte blockcopolymers, were preserved on the basis of shorter-rangeintramicellar interactions.

The controlled stacking of polymeric micelles was studiedusing conventional bright-field transmission electron microscopy(TEM) and cryoTEM images. Polymers used in this study arelisted in Chart 1. The effect of block copolymer architecture informing different stacking structures was examined using twodifferent triblock polymers, PAA99-b-PMA73-b-PS203and PAA94-b-PMA104-b-PS88 designated S203 and S88, respectively. Inaddition, two diblock copolymers with a fixed PAA chain lengthof 99 and a PS chain length of either 76 or 177, designated DS76and DS177, respectively, were used to form stacks from a simplediblock copolymer mixture. The use of these block copolymerswas based on studies of different micellar morphologies formedin the presence of 2,2′-(ethylenedioxy)bis(ethylamine) (EDDA,diamine).

Stacks of disks were obtained using S203 triblock copolymerbetween 30/70 and 50/50 H2O/THF with EDDA as the counterionat an overall amine/acid ratio of 1/1 (Figure 1). At water contentsbelow 30% in solution, bulk phase separation was observed. Atwater contents above 50%, discrete disks were obtained. Stacksof disks were stable in solution for at least several weeksand were observed to be kinetic pathway-independent; stackswere obtained either beginning from bulk phase-separatedregions (<30% water) by adding water to the system or begin-ning from discrete micellar regions (>50% water) by addingTHF to the solution. In addition, these processes were reversible.Using both pathways, stacks of disks that were micrometersin length along the stacking axis could be formed (Figure 2),and disks within the stacks, particularly nearest-neighbordisks along the stacking direction, were uniform in size. Discretedisks were not uniform in size at high water content, but theyformed well-organized stacks having uniform sizes whenTHF was added to the solution to reach the stable stackcomposition.

Bifunctional amine counterions (EDDA) were considered toplay an important role in bridging together corona blocks of

Figure 2. Stack of disks can be micrometers in length. (Top) TEM micrographs show stacks of disks micrometers in length along the stackingaxis in which disks within the stacks, especially nearest-neighbor disks along the stacking direction, are uniform in size. (Top inset) Cryo-TEMmicrograph of a stack of disks in solution. (Bottom) Schematic of intermicellar polymer chain transfer to reach disks with uniform diameters.

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neighboring micelles through either electrostatic or hydrogenbonding interactions between PAA and two amine functionalend groups. In an effort to understand the effect of diamine inthe stacking process, a small amount of monoamine was addedto discrete micelle solutions to interact with micelle surfaces.Monoamine (2-aminoethyl methyl ether) with a 0.1:1 amine/acid ratio was added to the micelle solution with a 1:1 amine/acid ratio with diamine, at ca. 70% water. This high water contentsolution contained discrete disks. The monoamine addition wasfollowed by the addition of THF to access the stack-phase regionat ca. 40% water. No stacks of disks were obtained, whereasunder these conditions in the absence of the monoamine, stackeddisks were predominant. This result indicates that interactionsbetween corona PAA blocks mediated by diamines dictated thestacking process, whereby it is expected that two amine functionalgroups of the same diamine interact with two acid functionalgroups from neighboring but different micelles through elec-trostatic interactions. Similar amine-to-PAA interaction haspreviously been observed within the same micelle, in which themicelle geometry can be successfully adjusted through the typeand amount of diamine counterions.21The cryoTEM micrographin Figure 2 confirmed the presence of stacks in solution, anddistances between individual disks are appropriate for the stronginteraction of corona blocks on neighboring micelles. In thecryoTEM micrograph, dark regions are the hydrophobic micellecores, and the areas between the micellar cores are solvated

hydrophilic corona blocks. It is also interesting that stackingalways occurred in solutions containing approximately 40% water,for which the dielectric constant is lower than that of higherwater content solutions. The role of strong electrostatic interac-tions in nonpolar solvents has recently been discussed by theWeitz group,22 and as the THF content increases in the systemstudied here, the diamines would be able to bridge two disksmore effectively than those in higher water content, higherdielectric constant solvent samples. Stacks observed from highwater composition solutions (micelles) can be considered to haveformed from a two-step self-assembly process through whichmicelles self-assembled into regularly stacked structures andthen subsequent intermicellar polymer exchange23 occurredbetween disks to produce uniform disk sizes. The intermicellarpolymer exchange becomes possible after the micelles havestacked, and self-sorting of disks with similar sizes to find eachother in solution to form stacks was considered to be less feasible.Similar stacking structures were previously obtained by Harrisfrom a zwitterionic surfactant,L-R-lysophosphatidylcholines,24

with similar geometry but on a much smaller length scale ascompared to those afforded from block copolymers.

(22) Hsu, M. F.; Dufresne, E. R.; Weitz, D. A.Langmuir2005, 21, 4881-4887.

(23) Tian, M.; Qin, A.; Ramireddy, C.; Webber, S. E.; Munk, P.; Tuzar, Z.;Prochazka, K.Langmuir1993, 9, 1741-1748.

(24) Harris, J. R.Micron Microsc. Acta1986, 17, 289-305.

Figure 3. TEM micrographs of cylinder-like (cylinders and Ys) stacked structures. (Top) Stack of cylinders and Ys obtained from S203triblock copolymers in a 40%water/THF mixture with a 2:1 amine/acid ratio. (Bottom left) Stacks of cylinders containing trifunctional branchpoints. (Bottom right) Stacks of cylinder-like micelles obtained from S88 triblock copolymers in a 40% water/THF mixture with a 1:1amine/acid ratio.

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Similar to the stacks of disks, stacked Ys and linear cylinders(Figure 3) were also observed and were stable in solution forweeks. S203 triblock copolymer with an amine/acid ratio of 2:1was used to study the stacking of structures that occurs at asolvent composition between bulk phase-separated block co-polymer precipitate particles and discrete cylindrical micelles.A different triblock copolymer, S88, having a shorter PS chainlength at an amine/acid ratio of 1:1 could also form stacks ofcylinders and Ys. In contrast to the broad range of conditionsunder which stacked disks could be formed, the stacked cylinder-like structures (Ys and cylinders) could be obtained only byadding water to the bulk phase-separated region of the phasediagram (<30% water). No stacking or similar organization wasobserved while adding THF to water-rich cylindrical micellesuspensions (>50% water). The kinetic pathway dependenceduring the stacking of cylinder-like micelles indicates a weakerintermicellar interaction between cylinders than between disksbecause of the smaller surface area of the cylindrical morphologyin comparison to the large surface contact area available forintermicellar disk interactions. The cylinder-like micelles werefound to preserve their regularity over micrometers in lengthalong the stacking axis, while hierarchically stacked together.

Disk-to-cylinder micelle intermediates, undergoing micellarassembly transformations, have been captured previously by add-ing additional diamine counterions to solutions of disks or bychanging the solvent composition.21Interestingly, stacks of disk-to-cylinder intermediates observed in the current study could bereproducibly formed through an increase in the diamine content

of a stacked disk solution originally formed using S203 at a 1:1amine/acid ratio and ca. 40% water in a water/THF solution.Figure 4 contains stacks of disk-to-cylinder intermediates. Thetransformation of disks into cylinders seemed to occur all alongthe stacking directions, thus producing stacks of disk-to-cylinderintermediates. This experimental result indicates that the interac-tions between micelles within stacks can be micrometers in lengthand stable during the kinetic process of micelle geometrytransformation.

Stacking of polymer micelles is not unique to triblock copoly-mer architectures and was also observed from diblock copolymermixtures. Physical mixtures of PAA-b-PS diblock copolymershaving the same PAA chain length and different PS chain lengths,DS76 and DS177, were used to apply intramicellar segregationin order to obtain disk-shaped structures. Intramicellar segregationof block copolymer molecules has been predicted25 and recentlyobserved experimentally.26 Disks contain an edge region withhigh interfacial curvature, which is more easily populated byshorter PS chain length diblock copolymers, and a disk centerwith low interfacial curvature, which favors population by longerPS chain length diblock copolymers. DS76 and DS177 individu-ally form cylinders and vesicles, respectively, at a ca. 70% water/THF solution composition. Remarkably, in the diblock copolymermixture (20 wt % polymer was DS76 and the remaining 80 wt% was DS177), stacks of disks were observed in solution THF/water compositions between those that produce bulk phase sepa-

(25) Halperin, A.J. Phys.1988, 49, 131-137.(26) Jain, S.; Bates, F. S.Macromolecules2004, 37, 1511-1523.

Figure 4. TEM micrographs of different stacks during disk-to-cylinder transformation. S203 copolymer solutions formed stacksof disks initially at a 1:1 amine/acid ratio, followed by an increasein diamine composition to a 2:1 amine/acid ratio at 40% water/THF.False colors are used to highlight different stacking structures.

Figure 5. TEM (top) and cryo-TEM (bottom) micrographs of stacksof disks observed from PAA-b-PS diblock copolymer mixtures (20wt % was DS76 and the remaining 80 wt % was DS177) in a 40%water/THF mixture with a 0.3:1 amine/acid ratio.

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ration and micellization (Figure 5). Whereas the stacks formedfrom diblock copolymer mixtures do not extend over distancesas long as those observed in the S203 triblock copolymer systems,the diblock copolymer blend stacks are also stable for many weeks.

In summary, stacks of polymer micelle assemblies in solutionhave been observed in both triblock copolymers and diblockcopolymer mixtures. Stacks of disks could be obtained by eitherwater addition to low water content bulk phase-separated polymersuspensions or THF addition to water-rich micelle suspensions,which are processes that reveal the disk-stacking process to bereversible. Whereas individual disks were heterogeneous in sizeat high water composition, the disks within stacks were uniformin size after stacking, which is hypothesized to be due tointermicellar polymer exchange. The interactions betweencylinder-like micelles were not strong enough to form stacksfrom the discrete micellar region, but stacks of cylindrical micellescould be captured by starting from bulk phase-separated droplets.Stacks of cylindrical structures were stable in solutions for weeks.Individual disks in the disk stacks could be transformed intocylinders by increasing the diamine concentration. The trans-formation of the disks into cylinders seemed to occur all alongthe stack of disks, thus producing a stack of organized disk-to-cylinder intermediates with similar morphology.

These stacked assemblies of nanoscale micellar assembliesrepresent unique hierarchical structures. Further elucidation ofthe mechanisms by which such materials can be afforded,expansion of the compositions and structures that can employed,

and extension into other unique morphologies represent ongoingwork that is expected to advance these materials toward enhancedhomogeneity of structural sizes and morphologies and investiga-tions into their potential applications. Remarkably, it has alsobeen found that triblock copolymers are not required to achievethe intermicellar assembly of these interesting disk-shapednanoscale assemblies, but rather stacks of disks formed evenfrom simple diblock copolymer mixtures. Key parameters inmicelle stacking include the appropriate balance of solvent/nonsolvent conditions and the presence of diamine to allow forintra- and intermicellar attractive interactions within and betweenthe acrylic acid polyelectrolyte micelle shells.

Acknowledgment. This material is based upon work sup-ported by the National Science Foundation under NSF-NIRTgrant no. DMR-0210247 and NSF grant no. 0451490. D.J.P.also acknowledges a DuPont Young Faculty Award for support.W. M. Keck College of Engineering electron microscopy lab atthe University of Delaware is also acknowledged. We thank J.L. Turner for the creation of the disk schematic in Figure 1. Wealso thank Dr. Chaoying Ni and Frank Kriss for their help duringthe TEM measurements.

Supporting Information Available: Further experimentaldetails and TEM preparation. This material is available free of chargevia the Internet at http://pubs.acs.org.

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