The association of di- or multiblock polymers in aqueous solution can result in the assembly of nanoobjects, such as micelles, liposomes or vesicles. RAFT polymerization is a particularly versatile synthetic method for building micellar assembles as it is applicable to a wide range of monomer structures (charged, zwitterionic, noncharged)406 with more versatility than ATRP or NMP. As there are a large number of references in this domain, we decided to restrict this review to the most recent examples detailed in the literature. For a detailed review in this area, the readers are invited to read the following reviews.33, 62, 406, 407
Micelle assembly and disassembly can be induced by the application of external stimuli, such as temperature, electrolyte concentration, or pH.33 Micelles can be used as nanoreactors for the synthesis of inorganic compounds or for specific organic reactions.408, 409 Liu and coworkers408 prepared different micelles using double hydrophilic block copolymers, based on poly(NIPAAm)-b-poly(N-vinylimidazole)). The poly(N-vinylimidazole) block catalyzed the esterolysis reaction, while the poly(NIPAAm) block induced micellization stimulated by a change in temperature.
Micelles for drug delivery applications structures have been described using RAFT polymerization.407, 410 For drug delivery applications, micelles are generally targeted with sizes below 200 nm, to avoid elimination by phagocytes and allowing for accumulation in vivo by the enhanced permeability and retention (EPR) effect.411, 412 CAMD researchers have described micelle structures bearing surface sugar moieties based on diblock poly(diethylene glycol-methacrylate- b-hydroxy ethyl methacrylates) (poly(DEG-MA-b-HEMA)) copolymers,104 where the pendant hydroxyl groups were modified into alkene groups by reaction with pentanoic acid, followed by a thiol-ene reaction to introduce sugar moieties on the backbone. The second block DEG-MA exhibited a LCST of 29 °C driving self-assembly. Interesting, the glucose decorated micelles presented a higher binding rate with Concanavalin A, when compared to equivalent linear polymers. Hydrophobic cores can be exploited for the transport and the encapsulation of hydrophobic drugs, such as doxorubicin, prednisone acetate, and paclitaxel for example. Wang and coworkers413 synthesized triblock poly(caprolactone)-b-poly (NIPAAm)-b-poly(caprolactone) copolymers using a combination of ROP and RAFT polymerizations. The resultant copolymers were self assembled into micelles, with an hydrophobic core based on poly(caprolactone), and a hydrophilic shell based on poly(NIPAAm). The core was used to encapsulate prednisone acetate, subsequently the release of this drug was observed by an increase in temperature (Fig. 1). In another study, Gao and coworkers414 used diblock PMMA-b-(OEG-A-co-NIPAAm)-b-PMMA copolymers for folic acid delivery. Micelles have also been used in vitro for the delivery of anticancer drugs.410 For example, paclitaxel was encapsulated into poly(2-methacryloyloxyethyl phosphorylcholine)-b-poly(nBuA).
Figure 1. Synthesis of thermo-responsive micelle for drug delivery. (a) Schematic representation; (b) Release of model drug versus temperature and time (h). Reproduced from ref.413, with permission from Journal of Polymer Science: Part A: Polymer Chemistry.
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For use in vivo, micelles need to be stabilized to prevent disassembly. Thus stabilization via cross-linking has become an area of intense investigation. Different pathways to stabilize micelles have been reported, such as chain extension in the presence of cross-linker415 or functional groups416, 417 in the core or shell.
To facilitate removal of the polymer (postdelivery) by the renal system, biodegradable cross-linking strategies have been developed. Different pH-sensitive cross-linkers have been developed using acetal and ketal groups to yield pH-sensitive nanoparticles (Scheme 15).418, 419 Redox-sensitive micelles have also been developed via chain extension using a cross-linker bearing a disulfide bond420, 421 or by postmodification of polymers.422, 423 In the presence of a reducing agent, such as glutathione, disulfide-stabilized micelles disassemble into unimers, thereby releasing their drug payload. pH-sensitive micelles can liberate drugs in the endosome, while redox-sensitive micelles liberate drugs in the cytoplasm. McCormick and coworkers114, 424, 425 synthesized PEO-b-(DMA-s-NAS)-b-NIPAAm triblock copolymers (with NAS: N-acryloxysuccinimide) thereby yielding micelles above 37 °C (Scheme 16). The presence of NAS was exploited to cross-link the micelles using cistamine, a disulfide based difunctional amine, resulting in micelles that could be disassembled by reduction of disulfide bonds, but subsequently reassembled on exposure to air. Click chemistry using a disulfide containing difunctional azide has been employed to stabilize micelles loaded with cobalt drugs.426 Degradable micelles have also been obtained by cross-linking micelles with a Pt(IV) containing cross-linker, clicked onto the polymer backbone via isocyanates. In the cytoplasm, the crosslinked micelle is cleaved into its constituent block copolymers, releasing Pt(IV). Subsequently, Pt(IV) is reduced to its active form Pt(II).417
Scheme 15. Synthesis of pH-sensitive cross-link micelles for drug delivery application. Reproduced from ref.418, with permission from American Chemical Society.
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Targeting agents such as peptides, antibodies, or sugar moieties, can be conjugated to micelle surfaces.427 Alternatively, end groups can be exploited to introduce targeting agents. Liu et al.226 synthesized micelles decorated with pyridyl disulfide end groups for subsequent modification with a model peptide or thio-rhodamine. The presence of trithiocarbonates at the surface of micelles can be exploited for functionalization as illustrated by Perrier and coworkers,428 who proposed a one-pot approach to the cross-linking and modification of micelles using NHS/amine coupling and thiol-ene reactions. In another example, Sumerlin and coworkers used an azide-alkyne reaction to attach folic acid at the surface of micelles.239
While most cross-linking techniques utilize the presence of functional groups on either the core or the shell forming block, the RAFT process itself opens up a further avenue to obtain crosslinked micelles. The presence of the thiocarbonyl functionality at the surface of the micelle or the core of the micelle can permit chain extension, where self-assembled micelles are mixed with divinyl compounds with subsequent polymerization leading to shell or core cross-linking.303, 421, 429 Core-cross-linking with diacrylates is usually highly efficient while reaction with divinyl benzene can be sluggish.430 Degradability of micelles can be achieved by introducing either pH-degradable functional groups or disulfides. A drawback of chain extension with divinyl compounds is the formation of intermicellar crosslinks.431 Emulsion-based chemistry using a chain extension cross-linking approach has been exploited to generate well-defined, highly bioactive, core-shell glyco-nanoparticles (Scheme 17).432
A cross-linking approach to nanoparticle formation can also exploit the RAFT functionality at the nexus of two blocks in a block copolymer. In this ‘nexus’ approach, a polylactide-based RAFT agent – formed by the ring-opening polymerization of 3,6-Dimethyl-1,4-dioxane-2,5-dione by a functional RAFT agent – was used to polymerize NIPAAm or a glycomonomer.433, 434 As the thiocarbonylthio group was situated between the blocks, the subsequent cross-linking process via RAFT resulted in cross-linking at the interface between core and shell. This “nexus” cross-linking approach yields better phase separation between core and shell,434 and also offers the opportunity to selectively remove the polylactide core creating hollow nanocages.433
Vesicles and More Complex Architectures
Under certain conditions, amphiphilic polymers can self-assemble into specific, complex structures, for example, vesicles or rod structures.435–437 The hydrophilic/hydrophobic balance and the method of preparation can dictate the formation of these specific architectures.438 Eisenberg and coworkers439, 440 have described the morphology evolution dependent on the molecular weight of the hydrophobic block and the nature of the hydrophilic block (charged or noncharged). The polymer concentration and the presence of cosolvents can also affect the morphology of amphiphilic polymer assembly.436, 441, 442
Responsive block copolymers can also be used in the preparation of complex architectures, such as vesicles.76, 415, 431, 443 McCormick and coworkers444 exploited a dually responsive poly(DEAEMA-b-NIPAAm) copolymer capable of "schizophrenic" aggregation in aqueous solution (Fig. 2). The nano-assembly, dictated by the hydrophilic mass fraction, was controlled by the polymer block lengths, by pH, and temperature. Both poly(DEAEMA-b-NIPAAm) (52.5 wt % NIPAAm) and poly(DEAEMA-b-NIPAAm) (70.8 wt % NIPAAm) self-assembled into poly(DEAEMA)-core poly(NIPAAm)-shell spherical micelles with hydrodynamic radii (Rh) of 21 and 25 nm, respectively at temperatures below the LCST of poly (NIPAAm) and at pH values greater than the pKa of PDEAEMA. However, the two block copolymers displayed quite different temperature responsive behaviors at pH < 7.5. At elevated temperature (>42 °C) poly(DEAEMA98-b-NIPAAm209) formed spherical micelles (Rh = 28 nm) with hydrophobic poly(NIPAAm) cores stabilized by a hydrophilic PDEAEMA shell. In contrast, poly(DEAEMA98-b-NIPAAm392) assembled into vesicles (Rh = 99 nm) above 38 °C. Different strategies to cross-link “schizophrenic” structures have been developed to lock in place these unique structures.445
Figure 2. Synthesis of vesicle by self-assembled of pH-sensitive and thermo-sensitive polymers. Reproduced from ref.444, with permission from American Chemical Society.
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Huang and coworkers446 studied the effect of block molecular weight of PEO and PSt in a (PEO-b-PSt)x multiblock copolymers on the self-assembly behavior. Long rods were observed for a composition containing 23 mol % of PEO and 77 mol % of PSt, however, when PEO was increased to 25 mol %, the polymers formed octopus-like structures, while below 20 mol % PEO, large micelles were observed.
Self-organization of polymers in aqueous media into higher nanostructures can also be driven by end groups.447–449 Moughton and O'Reilly450 introduced a quaternized amine as an end group to poly(NIPAAm-b-tert-BuA) synthesized by RAFT polymerization. Below the LCST of poly(NIPAAm), the copolymers generated micelles with a poly(NIPAAm) shell, while above the LCST, the poly(NIPAAm) became hydrophobic driving a reorganization of the micelle into vesicles. Recently, CAMD451 has prepared spherical and tubular vesicles from hydrophilic homopolymers of N,N-dimethylacrylamide (DMA) and N-(2-hydroxypropyl) methacrylamide (HPMA). These homopolymers were obtained using new RAFT chain transfer agents containing one to four hydrophobic functional groups in the R fragment based on pyrene, cholesterol, or octadecane, resulting in hydrophilic homopolymers containing a low proportion (6–23 wt %) of hydrophobic end groups. Poly-DMA and poly-HPMA homopolymers, of varying molar masses with either bis pyrenyl or cholesteryl end groups self-assembled in aqueous media forming spherical vesicles with sizes in the range of several hundred nm up to about 1 μm. These polymersomes are also able to sequester the hydrophilic compounds.
Recently, Pan and coworkers452, 453 proposed a one-pot approach to polymeric nanomaterials via RAFT polymerization in dispersed media. The authors used a macro-RAFT agent (PVP-RAFT) initially soluble in methanol for the polymerization control of styrene. As conversion increased, phase segregation occurred driven by the poor solubility of the PSt block. Different morphologies from vesicles453 to nanowires454 were obtained depending on the initial [St]0 : [macro-RAFT]0 ratio and the conversion of styrene. In addition, this technique allows the synthesis of multimorphologies (vesicle, nanorods, nanotubes and doughnuts) in a very high concentration as high as 500 mg/mL.452 Recently, Charleux and coworkers455 proposed an emulsion RAFT polymerization route to yield nanofibers, by copolymerization of AA and OEG-A in ethanol at 70 °C. In a second step, poly(AA-co-OEG-A) was then dispersed in basic aqueous media, and the copolymer was chain extended in the presence of styrene to generate nanofibers. The chain extension of poly(AA-co-OEG-A) using styrene as monomer in water results by the formation of insoluble PSt block. These insoluble blocks self-assembled in water to yield nanofibers. This novel emulsion process directly allowed the synthesis of nanofibers at very high concentration of polymer (11 wt %). In addition, a similar result was obtained when the diblock copolymer was self-assembled by continuous addition of water. Armes and coworkers used a similar process to obtain nanoparticles of poly(GMA-b-hydroxyl propyl methacrylate).456
Synthesis of Hybrid Nanoparticles
(a) Grafting From and Onto
The modification of nanoparticle surfaces using RAFT polymers can be achieved using two alternative pathways: grafting from or grafting onto. Grafting “to” uses preformed polymers, while grafting from involves the growth of polymer chains from a surface. Both methods have advantages and disadvantages, for instance, the control of polymer architecture (functionality, composition) is superior when grafting “to” is used, however, the density of polymer chains is more difficult to control. In grafting from the RAFT functionality can be attached via the R or Z groups. The Z approach can be limited by steric hindrance of polymers already grafted onto the surface. The attachment by Z group also confers some instability on the composite material because of the potential for hydrolysis or aminolysis of the RAFT functionality. However, the R approach also has some limitations, with an increased possibility of radical coupling.
The topology of the nanoparticle surface can also have a great influence on the packing density of brushes, as flat and spherical surfaces present different deflection angles. Small nanoparticles can be more amenable to higher grafting densities as they display higher deflection angles.457
(b) Layer-by-layer methodology
Polymer modification of nanoparticle surfaces can also be achieved using a layer-by-layer methodology (LbL).458 This approach has been successfully employed for the modification of a large variety of nanoparticles, such as silica,459 gold,460, 461 iron oxide nanoparticles.462 In LbL, the polymer layers are physio-absorbed at the surface of the nanoparticles by electrostatic interactions or hydrogen bonding, resulting in the formation of thin films (Fig. 3). The thickness of the LbL film can be easily controlled by the deposition process. In addition, the permeability and the functionality of the films are dictated by the nature of the interactions. For example, films cemented by hydrogen bonding are responsive to environmental pH or temperatures. Hydrogen bonding between DNA base pairs allows multilayer films to disassemble when exposed to low ionic strength solutions.463 To improve the mechanical properties and the stability of LbL assembly, layers can be cross-linked by thiol-ene464 or azide-alkyne465–468 click reactions. This cross-linking approach has been exploited for the formation of hollow polymer nanocapsules for drug and gene delivery applications.469 In addition, click reactions can be used to attach therapeutic compounds to nano- and microcapsules.470
RAFT and LbL methodologies have been combined for nanoparticle syntheses.66, 471 The self-assembly of poly(styrene sulfonate-b-poly(oligoethylene glycol acrylate) (PSST-b-POEG-A) diblock copolymers on the surface of silica conferred antifouling properties at the nanoparticle surface.472 CAMD researchers exploited a LbL strategy to decorate gold nanoparticles with sugar moieties or with PEG polymers.108, 298
Carbon Nanotubes, Nanodiamond and Graphene
Since the discovery of graphene by Geim and coworkers in 2004,473 it has been touted as a “next generation material” because of its remarkable electronic, optical, and thermal properties, chemical and mechanical stability, and large surface area for applications in both emerging and conventional fields, such as field-effect transistors, sensors, electrochemical devices, electromechanical resonators, polymer nanocomposites, batteries, capacitors, and light emitting devices.474–482 Despite extensive research, graphene-based materials are restricted for practical applications by problems with scalable dispersion and the long-term stability of sheet aggregates held together by Van Der Waals interactions.483 Some problems may be overcome by the manufacture of polymer-graphene hybrids for obtaining highly stable colloidal suspensions of graphene properties. In addition, the addition of graphene into polymer blends result by an enhancement of mechanical and electronic properties. Carbon nanotube/polymer hybrids have also attracted interest for gene delivery. It was demonstrated that carbon nanotubes can pass through cell membranes,484–486 and accumulate in the nuclei of cells.486
RAFT-polymers may be attached onto carbon surfaces in several ways.487 The treatment of graphene and carbon nanotubes with HNO3 results in carboxylic acid functionality suitable for anchoring RAFT agents or polymer.68, 485, 488, 489 RAFT agents attached via the R group have been shown to control the polymerization of different monomers from nanotube surfaces.68, 490 In addition to grafting from, grafting onto has also been reported for the modification of nanotubes, using pyrene terminated polymers. The π interactions between pyrene and nanotube surfaces enable the attachment of polymers.491 This method has also been used successfully for graphene.492, 493 The functionalization of graphene by different charged polymers was exploited using a layer-by-layer process resulting in the formation of well organized graphene sheets.492, 494 Another approach to functionalize graphenes, nanotubes or nanodiamonds is to exploit the presence of carboxylic acid groups at their surfaces for LbL assembly to yield a thin film of polymers. Narain and coworkers495 attached sugar modified poly(2-aminoethyl acrylamide) (poly(AEA)) onto nanotubes surfaces using NHS/amine coupling reactions for gene delivery (Scheme 18). Recently, the modification of nanodiamonds was achieved by RAFT polymerization using the grafting onto approach. He and coworkers496 exploited the presence of carboxylic acid groups at the surface of nanodiamonds to attach a triblock poly(tert-Bu A)-b-(GMA-b-St) copolymers using a carboxylic acid and epoxy reaction.
Scheme 18. Modification of carbon nanotubes using RAFT polymerization for DNA delivery. Reproduced from ref.495, with permission from American Chemical Society.
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Metallic and Oxide Nanoparticles
Silica and titanium oxide nanoparticles can make solid supports with good chemical resistance at a reasonable cost for a large range of applications.497, 498 The attachment of polymer at the surface has been proposed to enhance applications in optics, bio-separations (purification), and electronics. Tsujii et al.499 reported the first surface-initiated RAFT polymerization to modify silica particles using a surface-anchored RAFT agent. Baum and Brittain200 utilized RAFT to graft polystyrene (PSt) and poly(methyl methacrylate) (PMMA) from silica particles using a surface-anchored azo initiator. Surface-initiated RAFT in the modification of silica nanoparticles has since been used with a wide range of polymers using grafting from or onto approaches.203, 215, 500–502 The attachment of polymers on silica surfaces can be achieved by different ways: (i) RAFT agent can be attached using a R approach onto the surface using a RAFT-silane coupling agent or using a coupling reaction between an activated ester RAFT agent and aminated silica nanoparticles, as suggested by Benicewicz and coworkers203, 215, 257, 503; (ii) RAFT agents can be attached using the Z group as proposed by Zhao and Perrier,501, 504 and others503; (iii) grafting of diblock copolymers, using poly(methacryloxypropyltrimethoxylsilane) to anchor the polymers.206, 505
In the recent works of Ranjan and Brittain,506 and Benicewicz and coworkers,257 surface-initiated RAFT polymerization was combined with click chemistry to modify the surface of silica nanoparticles through the use of an immobilized alkyne-terminated RAFT agent or azide pendant polymers. In other work, a new method for the modification of nearly monodispersed silica core-poly(N-vinylcarbazole) shell (SiO2 at PVK) microspheres was proposed by Kang and coworkers507 who described surface-initiated distillation-precipitation polymerization of N-vinylcarbazole in the presence of divinylbenzene from silica template microspheres prepared by the sol-gel reaction of tetraethyl orthosilicate (TEOS) and 3-(trimethoxysilyl)propyl methacrylate (MPP). SiO2 at PVK−PNIPAM core-shell hairy microspheres were subsequently prepared by grafting Poly(NIPAAm) chains, synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization to the SiO2 at PVK microspheres via thiol-ene click chemistry.
Iron Oxide Nanoparticles
Iron oxide nanoparticles (IONPs) can be applied to MRI imaging, drug and gene delivery, and hyperthermia treatment (Scheme 19).508–520 The magnetic properties of iron oxide or iron can be exploited to change the transversal relaxation time of surrounding water molecules in imaging or to guide nanoparticles in the body via an applied external magnetic field. However, iron oxide nanoparticles (and in general metallic or oxide nanoparticles) have poor stability in aqueous or organic solutions resulting in a rapid precipitation caused by their high surface energies (Scheme 20).520 Attaching organic compounds or polymers to the nanoparticle surface can help stabilize them in solution. The functionalization of IONPs can be carried out using a large range of anchoring functions, such as dopamine, carboxylic acid, phosphonic acid, and trimethoxysilane (Scheme 21).299
Lu and coworkers521 modified IONPs using a RAFT agent bearing a carboxylic acid, followed by the polymerization of NIPAAm to yield IONPs coated with poly(NIPAAm). Stayton, Narain et al. proposed the grafting ‘onto’ approach of biotin terminated poly(NIPAAm) to modify IONPs.522 The presence of biotin groups can be exploited for streptadivin conjugation. CAMD researchers147, 198 modified IONPs using preformed polymers bearing a phosphonic acid group and pyridyl disulfide end groups to stabilize IONPs in both aqueous solution and fetal bovine serum. The pyridyl disulfide end group was then exploited for the conjugation of peptides, while the phosphonic group was used to attach the polymers to the surface of iron oxide nanoparticles.198 Subsequently, two different polymers, that is, poly(OEG-A) and poly (DMAEA) were grafted onto the IONP surfaces. Poly(OEG-A) conferred an antifouling surface to the nanoparticles, while poly(DMAEA) was used to complex siRNA (Fig. 4).147
Figure 4. Modification of iron oxide nanoparticles using RAFT polymer for siRNA delivery: (a) schematic representation; (b) gel electrophoresis of siRNA complexed to IONPs; c) siRNA delivery to SH-EP cells before treatment and after treatment with siRNA/IONPs (note the expression of green fluorescence was knocked down by siRNA).
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The stabilization of iron oxide has also been achieved using diblock copolymers, with one block composed of carboxylic acid pendant groups to anchor to the IONP surface, and a second block to confer solution stability.523, 524 This strategy was successfully used for the attachment of nanotubes at the surface of IONPs.525
One interesting property of iron oxide nanoparticles is their ability to increase in temperature when exposed to a high frequency magnetic field. Narain and coworkers526 used this property to synthesize thermo-responsive IONPs coated with poly(NIPAAm). The authors show a reversible aggregation of these nanoparticles under a high frequency magnetic field by the LCST behavior of poly(NIPAAm).
Gold, Silver Nanoparticles and Quantum Dots
Gold and silver nanoparticles have numerous potential applications in a number of fields, viz, sensing,527 catalysis,528 nanomedicine527, 529–535 and chemical purification.268 However, in the absence of stabilizing agents, gold nanoparticles are unstable, aggregating and broadening their Plasmon resonance band. Stabilization using organic compounds, such as citric acid, is inefficient when gold nanoparticles (GNPs) are dispersed in saline solution or in serum, limiting potential applications in medical fields. The attachment of polymers can increase the stability of GNPs in saline aqueous solution or organic media, and can also confer new properties. A polymer shell can be used for the encapsulation of therapeutic compounds or for the attachment of targeting functions. “Grafting to” approaches almost exclusively employ the relatively strong Plasmon-gold536 or –silver537 interactions to bind Plasmon-terminated surfactant or polymers onto gold or silver surfaces, an approach well-suited to RAFT polymers. Thiol-modified gold colloids are very stable and behave as robust large molecules being amenable to characterization. In addition dithioester and trithiocarbonate can directly bind with gold (Scheme 20).93, 538, 539
The modification of gold nanoparticles with neutral, anionic, cationic, or zwitterionic presynthesized polymers is well established.540–544 Temperature-sensitive polymeric stabilizers have been extensively used for the modification of gold nanoparticles for sensing applications.93, 545–549 Poly(NIPAAm) homopolymers prepared using the RAFT technique with S-benzyl dithiobenzoate as the RAFT agent have been immobilized onto gold particles by the “grafting to” method following reduction of the dithioester end group with sodium borohydride to provide thiol groups. These thermo-sensitive hybrids retained the LCST of poly(NIPAAm) and exhibited a sharp, reversible phase transition in solution between 25 and 30 °C.550 The addition of salt was found to promote interparticle associations leading to a red shift in the Plasmon band and an increase in the hydrodynamic size, attributed to aggregate formation above the LCST.551 Recently, GNPs modified with thermo-responsive PEG obtained by RAFT copolymerization of OEG-A and DEG-A have been reported. According to the composition of the two monomers, the LCST of copolymers could be tuned from 20 °C to 95 °C. The thermo-sensitive nanoparticles were found to exhibit antifouling properties that were conserved above the LCST (Fig. 5). The self-assembly of two copolymers also facilitated the synthesis of gold nanoparticles presenting two different LCSTs.93 The bond stability between thiol and gold is reversible and is cleavable at high temperature (above 60 °C) reducing dramatically the potential application of these hybrid nanoparticles.552 To overcome this thermal instability problem, different strategies have been developed to cross-link polymer shells around GNPs. Recently, Hawker and coworkers self-assembled RAFT polymers bearing azide pendant groups on GNPs; after exposure to UV, the azide groups facilitated cross-linking by bimolecular coupling reactions.553
Figure 5. Grafting onto of poly(OEG-A-co-DEG-A) on gold surface to yield thermo-responsive nanoparticles: (A) schematic representation; (B) Evolution of I1/I3 of pyrene versus the temperature in the presence of GNPs/ Mixed polymers [poly(OEG-A)/poly (DEG-A-co-OEG-A)] = 50/50 wt %]; evolution of the gold particle sizes versus the temperature.
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Charged polymer modified gold nanoparticles have also been synthesized by the self-assembly of charged polymers. This type of charged hybrid can potentially be used for the transport of siRNA or DNA. The self-assembly of two different polymers, that is, one charged and one not charged but thermo-responsive, enables the tuning of charge using temperature (Fig. 6).540 Recently, McCormick and coworkers148 grafted charged/neutral diblock copolymer at the surface of gold nanoparticles. The cationic layer was used for encapsulating siRNA. These hybrid nanoparticles protected siRNA against nuclease attack and allowed the transport of siRNA to a number of different cell lines.
Narian et al.522, 554–556 synthesized gold nanoparticles decorated with sugar moieties and biotin groups for drug delivery and sensing applications using RAFT polymerization.
Finally, gold nanoparticles have also been used as sacrificial templates for the preparation of hollow nanocapsules by the dissolution of gold nanoparticles after polymer coating.557 To illustrate this example, CAMD558 used diblock poly(HPMA-b-(St-co-MA) obtained by RAFT polymerization to graft to gold surfaces (Fig. 7). Subsequently, a diamine was added to react with maleic anhydride present on the polymer backbone to induce cross-linking. Finally, the gold was dissolved using aqua regia reactant to leave nanocapsules.
Figure 7. Synthesis of nanocapsules using gold nanoparticles as sacrificial templates by grafting onto of poly(HEMA)-b-(ST-co-MA).
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Finally, quantum dots (QD) obtained from cadmium, zinc, selenium, telerium, and sulfur present a huge potential for imaging applications because of high fluorescence emission properties compared to traditional fluorophores, with a wide excitation and narrow emission window and resist photobleaching.559 The surface of QDs is usually composed of ZnS. The presence of ZnS can be easily modified by thiol terminated polymers.560 Thiol compounds can enhance the fluorescence of QDs by an order of magnitude.560 However, the interactions between thiol and QDs can be displaced by other thiols resulting in a loss of stability of QDs in biological media.561 For this reason, other strategies have been proposed to modify QDs. Liu et al.561 attached polymer-functionalized imidazole at the surface of QDs. The strong affinity of imidazole to QD surfaces resulted in the formation of inorganic/organic nanoparticles stable in biological media over a large range of pH. Emrick and coworkers562 synthesized a phosphine-functionalized RAFT agent able to bind onto QD surfaces. RAFT polymerization was successfully performed with a large range of monomers, such as styrene, methyl acrylate and butyl acrylate.