北京化工大学：《材料导论》课程阅读材料（高分子材料）Toward_mart nano-objects_by_self-assembly_of_bloc.pdf

Toward ‘smart’ nano-objects by self-assembly of block copolymers in solution J. Rodrı´guez-Herna´ndez, F. Che´cot, Y. Gnanou, S. Lecommandoux* Laboratoire de Chimie des Polyme`res Organiques, CNRS-UMR5629, ENSCPB, University Bordeaux 1, 16, Avenue Pey Berland, 33607 Pessac-Cedex, France Received 22 June 2004; received in revised form 9 April 2005; accepted 14 April 2005 Available online 12 July 2005 Abstract In recent years, the synthesis and analysis of novel copolymer-based nanomaterials in solution have been extensively pursued. The interest in such structures lies in the fact that their dimensions, in the mesoscopic range (!100 nm), and factors such as composition or structure lead to materials with singular properties and applications. In this article, we report the most significant developments in the preparation and characterization of nano-objects, presenting an organized and detailed overview of the state of the art. First, the basic principles of self-assembly and micellization of block copolymers in dilute solution will be discussed. A review of the methods for stabilization of the macromolecular aggregates will be then given, including selected recent examples. Finally, we will concentrate on stabilized nano-particles, so-called ‘smart materials’ that show responses to environmental changes (pH, temperature, ionic-strength, among others), focusing on their applications principally in the biomedical field. q 2005 Elsevier Ltd. All rights reserved. Keywords: Self-assembly; Micelle; Nano-objects; Block copolymers; Cross-linking; Stabilization; Stimulus; Smart Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 692 2. Self assembly—micellization of block copolymers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 695 2.1. Generalities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 695 2.2. Theoretical aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 696 2.3. Experimental aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 698 2.3.1. Preparation of micelles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 698 2.3.2. Formation of polymeric micelles: experimental determination of the CMC . . . . . . . . . . . . . . . . . 698 2.3.3. Characterization of micellar size and shape . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 699 Prog. Polym. Sci. 30 (2005) 691–724 www.elsevier.com/locate/ppolysci 0079-6700/$ - see front matter q 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.progpolymsci.2005.04.002 * Corresponding author. Tel.: C33 54000 22 41; fax: C33 54000 84 87. E-mail address: s.lecommandoux@enscpb.fr (S. Lecommandoux)

692 J.Rodriguez-Herdndez et al.Prog.Polvm.Sci.30(2005)691-724 2.4 8 2.4.2 icles 702 24.3 er morp Stahil 。 31 Stabilization via radical crosslinking polymerization 70 Polymerization of block-copolymer end-groups inside the micelle (Situation A)........ 313 3.14. Stabilization in bulk prior to micellization 707 3好 3.4 Stimulus-responsive nano-assemblies 3 42 Response to pH 43 714 Smart nano-objects Summary and outlook 719 1.Introduction monomers)used by nature.The developments achieved in the last decade in several chain-addition Very complex and diverse structures are con polymerizations [1-3]are just refinements of structed by nature from a reduced choice of methodologies of polymer synthesis,allowing better building units (amino acids,lipids,etc.).Proteins, control over composition,molar mass,and overall for instance.are formed from a few amino acids architectures,but by no means do they address an and exhibit different secondary conformations,e.g. assembly of structures of comparable complexity to B-sheet,or coiled.Proteins with well proteins!A recent approach,which is the motivation tertiary ternary stru are y.cells d peptide segments. and time consuming synthe re prod in large vanet gome by natu dres defined ie.not ch lie mers that should carry ah function (see Fig.1). info rmation to direct the self-assembly Contrary to macromolecules produced and used Furthermore,self-assembly of macromolecules pro by nature.synthetic polymers can be obtained from vides an efficient and rapid pathway for the a very large variety of monomers.Polymerization of synthesis of objects from nanometer to micrometer these monomers affords different kinds of more or range that are difficult if not impossible to obtain by less complex homopolymers and copolymers;and conventional chemical reactions.Depending on the macromolecular engineering of these gives access to morphologies obtained (size,shape,periodicity,etc. unusual architectures and shapes.However,none of these self-assembled systems have already been these structures exhibit the sophistication anc applied or shown to be suitable for a number of meric materials [5],electronics [6].drug delivery

2.4. Examples of micellar systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 699 2.4.1. Spherical micelles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 700 2.4.2. Vesicles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 702 2.4.3. Other morphologies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 703 3. Stabilization of self-assembled morphologies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 704 3.1. Stabilization via radical crosslinking polymerization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 705 3.1.1. Polymerization of block-copolymer end-groups inside the micelle (Situation A) . . . . . . . . . . . . . 705 3.1.2. Shell-crosslinking (SCL) (Situation B) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 706 3.1.3. Core-crosslinking (CCL) (Situation C) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 706 3.1.4. Stabilization in bulk prior to micellization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 707 3.2. Stabilization via chemical reaction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 708 3.3. Stabilization via H-bonding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 712 3.4. Stable objects via thermodynamic parameters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 712 4. Stimulus-responsive nano-assemblies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 713 4.1. Response to pH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 713 4.2. Response to temperature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 714 4.3. Multiresponsive systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 714 5. Smart nano-objects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 715 6. Summary and outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 718 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 719 1. Introduction Very complex and diverse structures are constructed by nature from a reduced choice of building units (amino acids, lipids, etc.). Proteins, for instance, are formed from a few amino acids and exhibit different secondary conformations, e. g. a-helix, b-sheet, or coiled. Proteins with welldefined tertiary and quaternary structures are constituted of folded peptide segments. Still higher in complexity, cells are produced in large variety by nature to address specific functions in the organism. Cell functions are fulfilled through the concerted action of few perfectly defined proteins, i.e. not every cell possesses the same proteins and only the appropriate ones can perform a determined function (see Fig. 1). Contrary to macromolecules produced and used by nature, synthetic polymers can be obtained from a very large variety of monomers. Polymerization of these monomers affords different kinds of more or less complex homopolymers and copolymers; and macromolecular engineering of these gives access to unusual architectures and shapes. However, none of these structures exhibit the sophistication and complexity attained by those derived from the combination of a mere 20 amino acids (natural monomers) used by nature. The developments achieved in the last decade in several chain-addition polymerizations [1–3] are just refinements of methodologies of polymer synthesis, allowing better control over composition, molar mass, and overall architectures, but by no means do they address an assembly of structures of comparable complexity to proteins! A recent approach, which is the motivation of the present review, looks into the possibility of reducing tedious and time consuming synthetic steps by engineering oligomers or polymers of relatively small size that can self-organize through purely physical forces (noncovalent forces) simulating the folding of peptide segments in proteins. The key point in this approach lies in the chemical structure of the synthetic oligomers that should carry all the information to direct the self-assembly process. Furthermore, self-assembly of macromolecules provides an efficient and rapid pathway for the synthesis of objects from nanometer to micrometer range that are difficult if not impossible to obtain by conventional chemical reactions. Depending on the morphologies obtained (size, shape, periodicity, etc.) these self-assembled systems have already been applied or shown to be suitable for a number of applications in nanotechnology [4], reusable elastomeric materials [5], electronics [6], drug delivery 692 J. Rodrı´guez-Herna´ndez et al. / Prog. Polym. Sci. 30 (2005) 691–724

[7], paints [8], cosmetics, lubricants, and detergents [9]. Among the various aggregation processes, the most extensively studied pertain to the self-assembly of block or graft copolymers. As a consequence of their molecular structure, block copolymers in the solid state form a variety of superlattices with sizes of a few nanometers, and nanoscale periodicities. The principles of such self-organization have been recently described by Fo¨rster and Platenberg [10], who underscored the simultaneous coexistence in such systems of two kinds of parallel forces. The first driving force consists in ‘long-range repulsive interactions’ between incompatible domains. For example, polystyrene-b-polyisoprene diblocks selfassemble in toluene into spherical micelles with a core of polyisoprene and a polystyrene corona [11]. In the case of amphiphilic diblock copolymers, containing a hydrophobic and a hydrophilic block, the repulsive interactions are due to the difference in solubility, and unlike block copolymers with both segments hydrophobic, the repulsion occurs for very short block lengths. The second class of interactions are defined as ‘short-range attractive interactions’ and are the Nomenclature AFM atomic force microscopy AMPS 2-acrylamido-2-methyl-1- propanesulfonate BIEE 1,2-bis (20 -iodoethoxyl) ethane CCL core crosslinking CMC critical micelle concentration CMT critical micelle temperature CSC core-shell-corona (micelles) DLS dynamic light scattering DSC differential scanning calorimetry HEC hydroxyethylcellulose LbL layer by layer (self-assembly) LCST lower critical solution temperature MD microdomain NCCM non-covalently connected micelles PAA poly(acrylic acid) PB polybutadiene PBLA poly(b-benzylaspartate) PBO poly(butylene oxide) PCEMA poly(2-cinnamoylethyl methacrylate) PCL poly(3-caprolactone) PCMMA poly(2-cinnamoylmethyl methacrylate) PDMA poly(2-(dimethylamino) methacrylate) PDEA poly(2-(diethylamino) methacrylate) PDMAEMA poly(2-(dimethylamino) ethyl methacrylate) PDEAEMA poly(2-(diethylamino) ethyl methacrylate) PDMS poly(dimethylsiloxane) PE polyethylene PEO poly(ethylene oxide) also referred to as poly(ethylene glycol) (PEG) PGA poly(L-glutamic acid) P(hCEMA) poly(2-hydrocinnamoyloxyethyl methacrylate) PI polyisoprene PIC polyion complex PLA polylactide PMHS poly(1,1-dimethyl-2,2-dihexylsilene) PMEMA poly(2-morpholino ethyl methacrylate) PMMA poly(methyl methacrylate) PPO poly(propylene oxide) PPQ-PS poly(phenylquinoline)-block-Polystyrene PS polystyrene PSMA poly(solketal methacrylate) PSS poly(styrene sulfonate) PtBA poly(tert-butyl acrylate) PTHPMA poly(2-tetrahydroxypyranyl methacrylate) P2VP, P4VP poly(2- or 4-vinylpyridine) PVPh poly(4-vinyl phenol) RG radius of gyration RH hydrodynamic radius SANS small-angle neutron scattering SAXS small-angle X-ray scattering SCK shell crosslinked knedels SCL shell crosslinking SLS static light scattering TEM transmission electron microscopy Z aggregation number J. Rodrı´guez-Herna´ndez et al. / Prog. Polym. Sci. 30 (2005) 691–724 693

consequence of a covalent bond linking the two blocks. The existence of this link between the two blocks is responsible for microphase separation, preventing the system from further separation on a macroscopic scale, as with polymer blends. Copolymers that self-organize in a selective solvent (for one of the two blocks) have found industrial applications, but one point of concern is the relatively poor stability of the aggregates formed. Several research groups have recently shown how to stabilize such structures irreversibly. Mainly based on crosslinking reactions, their strategies result in the formation of stable aggregates or objects that offer new applications [12]. In an attempt to gain in sophistication and find many more potential applications, micellar systems have been designed that are adaptable to their environment and able to respond in a controlled manner to external stimuli, i.e. synthesis of ‘nano-objects’ that exhibit ‘stimulus-responsive’ properties is a topic that gathers momentum, because their behavior is reminiscent of that exhibited by proteins. The design of synthetic structures that somehow approach proteins in their complexity, functionality, and performance is the basis of the present review. In this contribution, we will first discuss the micellization behavior of block copolymers and describe the most recent developments from both theoretical and experimental perspectives through selected examples. Our purpose is not to review this field exhaustively, but to recall the basic principles. In the second part, with a view to giving a complete account of the state of the art, we will report the most significant developments in the formation of nanoobjects, by self-assembly of diblock copolymers in dilute solution [13] followed by stabilization of the macromolecular aggregates. Next, we will focus on those nano-materials, also called smart-materials, that show response to given stimulus: pH, temperature, ionic strength, among others. The aim of this review is thus to give a detailed overview of recent advances in these promising fields. Finally, we will describe rare, recent examples of the most sophisticated systems, which can be referred to as ‘smart nano-objects’. These shape-persistent objects, formed by selfassembly and crosslinking of the morphology obtained, represent a new generation of robust and efficient containers that can respond to changes in their environment and appear suitable for a wide range of applications. Fig. 1. Schematic representation of diversity vs. complexity in natural and synthetic polymers. 694 J. Rodrı´guez-Herna´ndez et al. / Prog. Polym. Sci. 30 (2005) 691–724

2. Self assembly—micellization of block copolymers 2.1. Generalities Block copolymers consist of two- or morecovalently bonded blocks with different physical and chemical properties. Their ability to self-assemble both in solution and in bulk, and to generate a variety of microdomain (MD) morphologies (lamellae, hexagonally packed cylinders, body-centered cubic (bcc) spheres, gyroids, etc.) is well documented. Several books and review papers that address the selfassembly of block copolymers [13,14] have been published in the last few years. One special class of block copolymers of particular relevance for this review are so-called amphiphilic block copolymers. According to the common defi- nition, amphiphilic molecules (from Greek, amphi both and philic attraction) have affinities for two different environments. The two blocks in the latter case are not only incompatible, but they interact very differently with their environment due to their chemical nature and behave distinctively in solution (selective solvent). These differences can induce microphase separation of amphiphilic block copolymers, not only in aqueous media but also in organic solvents [15]. Block copolymers undergo two basic processes in solvent media: micellization and gelation. Micellization occurs when the block copolymer is dissolved in a large amount of a selective solvent for one of the blocks. Under these circumstances, the polymer chains tend to organize themselves in a variety of structures from micelles or vesicles to cylinders. The soluble block will be oriented towards the continuous solvent medium and become the ‘corona’ of the micelle formed, whereas the insoluble part will be shielded from the solvent in the ‘core’ of the structure (see Fig. 2). In contrast to micellization, gelation occurs from the semidilute to the high concentration regime of block copolymer solutions and results from an arrangement of ordered micelles. Two extremes of micellar structures can be distinguished for diblock copolymers, depending on the relative length of the blocks. If the soluble block is larger than the insoluble one, the micelles (see Fig. 3) formed consist of a small core and a very large corona, and are thus called ‘star-micelles’. By contrast, micelles having a large insoluble segment with a short soluble corona are referred to as ‘crew-cut micelles’ [16]. Fig. 2. Illustration of (a) micellization at the critical micelle concentration and (b) gelation at high concentration from diblock copolymers. J. Rodrı´guez-Herna´ndez et al. / Prog. Polym. Sci. 30 (2005) 691–724 695