Responsive microgels are cross-linked and polymeric in nature. They swell/deswell in response to stimuli such as temperature and pH (Shi et al. 2014). “Nanostructure” is a term generally used for a material of nanodimension, such as nanorod and nanoparticle. The properties of nanostructures are entirely different from that of bulk materials. The properties of gold (Au) nanostructures are different from nanostructures of other metals because they absorb in water window region (Daniel and Astruc 2004, Gorelikov et al. 2004). Their quantum size properties are also better than other metals, which make them good catalysts and sensors (Daniel and Astruc 2004). Therefore, nanostructures of Au are very important. Microgels fabricated with nanostructures are termed as hybrid microgels. Microgels fabricated with Au nanostructures (Au-microgel) possess the properties of microgels as well as of Au nanostructures. Naked Au nanostructures coalesce with each other and form big particles. Thus, nanostructures lose their quantum size properties after aggregation. That is why Au nanostructures are stabilized by some stabilizing agents such as surfactants (Jain et al. 2014), block copolymers (Sakai et al. 2013), dendrimers (Wen et al. 2013), and microgels (Pich et al. 2006, Akamatsu et al. 2009, Carregal-Romero et al. 2009). Microgels are the best stabilizers among all stabilizers. Pendant groups of polymer microgels fix the nanostructures inside the network. The cross-linking of microgels also resists the movement of nanostructures from one sieve to another. In this way, Au nanostructures are found to be stable in microgels even after long time storage (Gorelikov et al. 2004). Microgels are composed of responsive polymeric units and Au nanostructures possess surface plasmon resonance (SPR) property. Therefore, Au-microgels are pH, temperature, ionic strength, and photo-responsive at the same time (Xiao et al. 2014). Owing to the responsive behavior of microgels, the SPR band of Au nanostructures can be modulated in visible, infrared, and microwave regions (Jones et al. 2003, Gorelikov et al. 2004, Budhlall et al. 2008). The hybrid microgels can be obtained by mixing Au nanomaterial and microgel dispersions or by synthesizing Au nanomaterial within microgels (in vivo synthesis). However, their synthesis within microgels is more advantageous than ex vivo synthesis because microgels control the size and size distribution of in vivo synthesized nanostructures. Thus, microgel is a good stabilizer for Au nanostructures because microgels increase the stability and scope of applications of Au nanostructures. Au-microgels have been largely used in drug delivery (Shiotani et al. 2007), catalysis (Carregal-Romero et al. 2010, Agrawal et al. 2013), biosensing (Zhang et al. 2012), and microlensing (Jones and Lyon 2003, Jones et al. 2003). Scientists reported many systems of Au-microgel. These systems are hybrid microspheres (Gorelikov et al. 2004, Mat Lazim et al. 2010), hybrid microgel rings (Agrawal et al. 2013), core-shell hybrid microgels (Shiotani et al. 2007), core-shell-shell hybrid microgels (Suzuki et al. 2007), and yolk-shell hybrid microgels (Carregal-Romero et al. 2010). They designed these systems for specific applications (Das et al. 2008, Carregal-Romero et al. 2009, Agrawal et al. 2013). Many review articles have been published on the subject of hybrid microgels, but all of them are general reviews. A little description on microgels fabricated with different metals is explained in all of those reviews. According to the best of our knowledge, no review article is available in the literature on Au-microgel. Therefore, all the aspects (synthesis, properties, characterization, and applications) of Au-microgel have not been deeply explained and correlated earlier. Therefore, there is a need to organize the recent literature of Au-microgels, so that scientists working in this area can plan their future work accordingly. Au-microgels have been used for photothermal therapy and drug delivery in mice. The basic mechanism has been explained here. Scientists can get dimension from this review to work on other animals that are closely related to humans, so that these hybrid microgels will be successfully used for mankind in the future. Similarly, hybrid microgels have been used as sensor and catalyst. Dimensions have been pointed out in this review to make a better sensor and catalyst in the future. That is why this review article is need of time.
The synthesis, classification, properties, characterization, and applications of Au-microgels are discussed in this review. A brief introduction of the topic is provided in Section 1. The classification and synthesis of Au-microgels are given in Sections 2 and 3, respectively. The mechanism of temperature, pH, photo-, and glucose-responsive behaviors of hybrid microgels is described in Section 4. The properties of hybrid microgels arising due to the presence of Au nanostructures are discussed in Sections 5 and 6. A comparison of different techniques used for the characterization of Au-microgels is given in Section 7. The applications of Au-microgels in biomedicine, sensing, catalysis, photonics, and coating are described in Section 8.
2 Classification of Au-microgels
Au-microgels are classified on the basis of position of nanostructures in microgels as hybrid microspheres, hybrid microgel rings, core-shell hybrid microgels, core-shell-shell hybrid microgels, and yolk-shell hybrid microgels (Table 1).
2.1 Hybrid microspheres
Au nanostructures are distributed in the whole polymer network in hybrid microspheres. Cross-linking density is uniform in the whole microgel particle (Table 1). Nanostructures are fabricated in the sieves of microgel particles. Hybrid microspheres swell/deswell abruptly because the distribution of monomers and nanostructures is uniform throughout the microgel particle. Gorelikov et al. (2004) and Shi et al. (2014) have reported the synthesis of hybrid microspheres for drug delivery and catalytic applications, respectively.
2.2 Hybrid microgel rings
Au nanostructures are uniformly fabricated in a ring-shaped microgel network. This hybrid system has gained attention, because ring thickness is very small and nanostructures come on surface in shrunken state easily. Lange et al. (2012) have synthesized Au-poly(N-isopropylacrylamide) [Au-p(NIPAM)] hybrid microgel rings in which Au nanoparticles are present in the p(NIPAM) network. Hollow space at the center is filled with solvent, so both the inner and outer surfaces of the ring are in full contact with the solvent. Moreover, the hollow space can act as a storehouse for drugs and other materials. These materials can be transported in large amount to target place via hybrid microgel rings. That is why this architecture of hybrid microgels is considered the most suitable for drug delivery.
2.3 Core-shell hybrid microgels
The structure of core is different from that of shell in these microgels. This is a versatile class of hybrid microgels. Various architectures of core-shell hybrid microgels have been synthesized by scientists whose detail is as follows.
Au nanostructure can act as core and cross-linked network can act as shell to form core-shell hybrid microgels (Budhlall et al. 2008). Center acts as plasmonic material and shell modulates the value of SPR wavelength (λSPR) by swelling/deswelling (Kim and Lee 2007). Kim and Lee (2006) have synthesized core-shell hybrid microgels for drug delivery; they used Au nanoparticle as core and synthesized poly(NIPAM-co-acrylic acid) [p(NIPAM-co-AAc)] microgels as shell. The catalytic activity of nanoparticles can be effectively controlled using this type of core-shell hybrid microgels because the catalyst is present at the center and the diffusion of reactants is controlled by shell. Carregal-Romero et al. (2010) have synthesized Au-p(NIPAM) core-shell hybrid microgels for catalytic applications. They controlled diffusion of reactants towards Au nanoparticle by modulating the cross-linking of p(NIPAM) shell. Shiotani et al. (2007) used Au nanorods as core and p(NIPAM) network as shell for photothermal drug delivery.
Nanostructures are present at the periphery of these microgel particles. Therefore, microgel acts as core and nanostructures act as shell. Kumar et al. (2007) have synthesized such core-shell microgels in which p(NIPAM) microgel particle is surrounded by Au nanorods. These hybrid microgels are most applicable in the field of photonics because nanostructures are present at the periphery only. Thus, the distance between nanostructures in swollen and deswollen state can be easily calculated.
Core and shell both are made up of cross-linked polymeric network, but Au nanostructures are uniformly fabricated in shell only. Suzuki and Kawaguchi (2005a,b) have synthesized such hybrid microgels. Poly(glycidyl methacrylate) [p(GMA)] acts as core and Au-p(NIPAM) acts as shell. Such hybrid microgels have not been used for any application yet, but they can be used in sensing and photonics.
Core and shell of this type are composed of cross-linked network, but Au nanostructures are present as layer at the core-shell interface only. Suzuki and Kawaguchi (2005a,b) have also synthesized these hybrid microgels. They synthesized poly(NIPAM-co-glycidyl methacrylate) [p(NIPAM-co-GMA)] microgels, then they used these microgels as seeds for the fabrication of p(NIPAM) shell, and then they fabricated Au nanoparticles at the core-shell interface.
2.4 Core-shell-shell hybrid microgels
The structure of core-shell-shell hybrid microgels is a modified form of core-shell hybrid microgels. When another layer of the polymer network is present around core-shell hybrid microgels, then core-shell-shell hybrid microgels are formed. All three layers are composed of polymeric network. These hybrid microgels are not suitable for photothermal drug delivery because nanoparticles are not distributed in the whole microgel particle. These hybrid microgels are suitable for catalysis and surface enhanced sensing. Suzuki et al. (2007) have prepared core-shell-shell hybrid microgels in which Au nanoparticles are fabricated in the middle layer only. Agrawal et al. (2013) also synthesized core-shell-shell hybrid microgels in which Au nanoparticles were present in core only and then they used these hybrid microgels for catalytic applications.
2.5 Yolk-shell hybrid microgels
This is also a modified form of core-shell hybrid microgels. In such kind of microgels, a space is present between core and shell. Core is composed of Au nanostructure and shell is composed of the polymer network. This architecture of hybrid microgel is most suitable for catalytic applications because the space around nanoparticle provides a homogenous environment of reagents for catalysis. The diffusion of reagents can be easily controlled with the help of microgel shell. Moreover catalyst dosage can be effectively controlled with yolk-shell architecture because one nanoparticle is present per hybrid microgel particle. Wu et al. (2012) have prepared Au-p(NIPAM) yolk-shell hybrid microgels for the catalytic reduction of 4-nitrophenol (4-NP) and nitrobenzene (NB). They also explained that these hybrid microgels are the best candidate for catalysis because reactants are present in the space between nanoparticles and polymeric network. Therefore, reactants are in full contact with nanoparticles and catalysis is done in an effective manner. Lange et al. (2012) have also synthesized Au-p(NIPAM) yolk-shell hybrid structures, but the shell thickness of their microgels is very small compared to those reported by Wu et al. (2012).
3 Synthesis of Au-microgels
3.1 Synthesis of microgels
Polymer network Au-microgels are synthesized by free radical precipitation and inverse emulsion polymerizations. Negative and positive temperature-responsive polymers are synthesized by precipitation and inverse emulsion polymerization, respectively (Echeverria and Mijangos 2010, Shi et al. 2013).
Precipitation polymerization for the synthesis of temperature-responsive microgels is carried out at a temperature greater than the volume phase transition temperature (VPTT) of the microgels in aqueous medium. If NIPAM is monomer, then the reaction mixture is heated up to 70°C in aqueous medium (Zhang et al. 2012). Monomers, surfactant, and cross-linker are mixed initially. Then, initiator (e.g. ammonium persulfate) is added. Initiator gives negatively charged free radicals. Free radicals have the ability to react with oxygen of air and reagents of the reaction mixture. The possibility of consumption of radicals by oxygen has terminated because the reaction is carried out under nitrogen atmosphere. Therefore, the radicals react with monomers and cross-linker and fabricate a cross-linked polymer network. The microgel dispersion is cooled and dialyzed using macromolecular porous membrane tubing. Dialysis is carried out for 7 days against distilled water at room temperature. Unreacted monomers are washed out from microgel dispersion by dialysis. Nearly monodisperse microgel particles are synthesized using this polymerization (Suzuki et al. 2007). The yield of product (microgel) depends on reaction time duration. A large amount of product (microgel) has been formed in initial first hour, but reaction is continued further only to maximize the amount of product.
Sometimes, microgels are coupled with some moieties that increase the scope of applications of microgels. For example, Shi et al. (2013) synthesized p(NIPAM-co-AAc) microgels and then they coupled carboxyl groups of AAc with 2-aminoethane thiol (AET) via 1-ethyl-3-[3-(dimethylamino)-propyl] carbodiimide hydrochloride. Coupling-modified microgels possess thiol at the tip of pendant group of AAc units. The authors then used these microgels as microreactors for the in vivo synthesis of Au nanoparticles. Then, the length of pendant group has increased after coupling. Therefore, it becomes easier to hold nanoparticle in place than that of noncoupled microgels. That is why the authors claimed that the AET pendant group has increased the stability of nanoparticles compared to that of carboxyl group. Similarly, Zhang et al. (2012) coupled p(NIPAM-co-AAc) microgels with 3-acrylamidophenylboronic acid (APBA) to make them glucose responsive. They also claimed that APBA has increased the stability of nanorods and the scope of this system for biomedical applications.
The morphology of microgel particles and distribution of monomer units inside the polymer network depends on the time of addition of monomers into reaction vessel. If all reagents are initially added, then they were incorporated homogenously in the polymer network. Gorelikov et al. (2004) have synthesized p(NIPAM-co-AAc) microgels by adding all monomers before the initiation of polymerization. If one monomer is added at one time and other is added later, then core is formed by monomer added first and shell is formed by monomer added later. Agrawal et al. (2013) added N-vinylcaprolactam (VCL), acetoacetoxyethyl methacrylate (AAEM), sodium dodecyl sulfate, and N,N′-methylene-bis-acrylamide (BIS) and initiated polymerization by adding initiator. After some time, they added AAc into reaction mixture. Thus, AAc resides in shell of the particles. They confirmed the core-shell structure of microgels by transmission electron microscopy (TEM) images. It is better to incorporate a thermoresponsive monomer at core and pH-responsive monomer at shell because the pH-responsive monomer causes greater swelling than that of thermoresponsive monomer. In this way, swelling due to the pH-responsive network is not hindered.
Microgels are also synthesized by inverse emulsion polymerization. For this purpose, emulsifier is added into organic phase. Monomers and cross-linker are dissolved in aqueous phase. Then, the aqueous phase is added dropwise into organic phase with constant stirring. The reaction mixture is heated up to a certain temperature depending on the monomers used. After some time, initiator is added. Initiator then initiated polymerization and turbidity is visible in the flask. Later, microgel dispersion is cooled and dialyzed against fresh water to remove unreacted reagents and organic phase. In this way, positive temperature-responsive microgels are synthesized by inverse emulsion polymerization. Echeverria and Mijangos (2010) have synthesized Au-poly(acrylamide-co-AAc) [Au-p(AAm-co-AAc)] core-shell hybrid microgels using this method.
3.2 Three approaches towards synthesis of Au-microgels
Au-microgels can be synthesized using the following methods.
3.2.1 Method of mixing of dispersions
When microgel dispersion is mixed with nanoparticle dispersion, then hybrid microgels are formed. Nanostructures may be symmetrically or asymmetrically distributed in the microgels depending on the method adopted for mixing of dispersions.
When microgel and nanoparticle dispersions are simply mixed, then nanostructures are symmetrically distributed within microgels under certain conditions of pH and temperature (Jones et al. 2003). Preformed nanoparticles have been stabilized with the help of surfactant, and surfactant molecules are charged. Both cationic and anionic surfactants have been used for the ex vivo synthesis of Au nanoparticles. Cationic surfactant helps to incorporate nanoparticles into negatively charged microgel, and anionic surfactant helps to incorporate nanoparticles into positively charged microgel. The negatively charged microgel attracts cationic surfactant-stabilized nanoparticles. Mostly acidic monomers are also present in the polymer network. Therefore, the polymer network becomes negatively charged due to the ionization of these acidic monomers at pH greater than the pKa of acidic units. Cationic surfactant-stabilized nanoparticles are attracted by negatively charged microgels. In this way, the attraction between acidic monomers and cationic surfactant ensure the loading of Au nanostructures within microgels. Many scientists have prepared hybrid microgels using this method (Pong et al. 2006, Davies and Vincent 2010, Gawlitza et al. 2013). Khan and Alhoshan (2013) have loaded cationic surfactant-stabilized Au nanoparticles into p(NIPAM-co-AAc) microgels. They reported that nanoparticles were diffused into microgel network due to the electrostatic attraction between cationic surfactant and carboxylate groups of microgel. Moreover, nanoparticles also moved into microgel due to centrifugation. Davies and Vincent (2010) loaded anionic surfactant-stabilized nanoparticle into positively charged poly(2-vinylpyridine) [p(2VP)] microgels. They studied the effect of pH on the loading of Au nanoparticles into microgel. They studied the loading of nanoparticles at pH 3 and 6. They observed that the loading of nanoparticles at pH 3 is greater than loading at pH 6, because p(2VP) microgels are cationic microgels and the size of microgel particles decreases with the increase in the pH of the medium.
Gawlitza et al. (2013) have reported the loading of Au nanoparticles within preformed p(NIPAM) microgels. They modulated the loading of Au nanoparticles by changing the cross-linking of p(NIPAM) microgels. They reported that the loading of nanoparticles has decreased by increasing the cross-linking of microgels.
For the asymmetric distribution of nanostructures inside the microgels, initially, microgels are dispersed in oil-in-water emulsion. Microgels adsorb at the oil-water interface. Then, the aqueous dispersion of Au nanostructures is added into this emulsion. As the half-surface of microgel is exposed to continuous phase, Au nanostructures are distributed on the hemisphere of microgels. Bradley and Garcia-Risueno (2011) have loaded Au nanoparticles within microgels asymmetrically using hexadecane-in-water emulsion.
3.2.2 Growth of Au nanostructures in the presence of preformed microgels
In this method, Au nanostructures are synthesized within preformed microgels. Here, microgels act as microreactors for the synthesis of nanostructures (Suzuki et al. 2014). For this purpose, Au salts such as chloroauric acid (HAuCl4) are added into positively charged microgel dispersion. Tetrachloroaurate (III) [AuCl4]1- diffuses into the microgel network due to electrostatic attractive forces. A reducing agent, such as sodium borohydride (NaBH4), is then added, which produces Au atoms. Then, Au atoms coalesce and produce Au nanostructures. Suzuki et al. (2014) have synthesized Au-p(NIPAM-co-3-(methacryl amino) propyltrimethylammonium chloride) hybrid microgels using this approach.
A slight modification in this approach has also been reported by Shi et al. (2014). Thiol group-functionalized microgels are used as microreactors in this approach. When [AuCl4]1- is added into microgel dispersion, then Au3+ is reduced into Au1+ thiolate with the help of thiol group. Then, a reducing agent (NaBH4) is added into the reaction mixture to convert Au1+ into Au0 atoms. Shi et al. (2014) have synthesized Au-microgels using this approach. They synthesized thiol-functionalized p(NIPAM-co-methacrylic acid) [p(NIPAM-co-MAAc)] microgels, and then they added [AuCl4]1- ions and NaBH4 into microgel dispersion and synthesized Au nanoparticles within microgels.
3.2.3 Growing microgel in the presence of preformed Au nanostructures
In this approach, the dispersion of Au nanostructures is prepared initially. Then, polymer microgels are synthesized in the presence of Au nanostructures using the method described in Section 3.1. Shiotani et al. (2007) fabricated the p(NIPAM) network around preformed Au nanorods. Carregal-Romero et al. (2010) and Jaber et al. (2011) have synthesized p(NIPAM) network around preformed Au nanoparticles.
4 Responsive behavior of Au-microgels
Microgels are responsive to various stimuli such as temperature, pH, and ionic strength. They swell/deswell in response to these stimuli. Au nanostructures absorb microwave, visible, and infrared radiations depending on their shape and size. Au-microgels are the combination of Au nanostructures and responsive microgel network, so they are responsive to pH, temperature, ionic strength, and light. Depending on the nature of monomers, microgels can be responsive to single or multiple stimuli at the same time. Like Au-p(NIPAM-co-AAc) hybrid microgels reported by Gorelikov et al. (2004), these hybrid microgels are responsive to many stimuli. They have reported pH, temperature, and infrared radiation-responsive behavior of these microgels.
The details of pH, temperature, glucose, and photoresponsive behavior of Au-microgels are as follows.
4.1 Temperature-responsive behavior
Microgels swell and deswell in response to the increase in temperature of the medium depending on the nature of the polymer network (Hou and Wu 2014). When Au nanostructures are loaded within microgels, then their temperature sensitivity does not vanish (Dulle et al. 2015). Hybrid microgels show temperature sensitivity similar to that of pure microgels. However, the VPTT of hybrid microgels is found to be different from that of pure microgels (Khan and Alhoshan 2013).
Based on the nature of temperature-responsive monomer, the responsive behavior of Au-microgels is classified as negative and positive temperature-responsive behaviors. The temperature-responsive behavior of both types of hybrid microgels has been discussed here in detail.
4.1.1 Negative temperature-responsive behavior
These hybrid microgels deswell at high temperature and swell at low temperature. The temperature at which swelling/deswelling transition occurs is termed as the VPTT. At low temperature, water-polymer interaction is stronger than polymer-polymer interaction. Therefore, water is present within microgels in large amount at low temperatures and causes swelling in microgels (Karg et al. 2010). As the temperature of the medium increases, then the hydrogen bonding of water molecules with pendant groups of polymer network is broken down. Polymer-polymer interaction becomes stronger than water-polymer interaction, so water is expelled out of microgels and they deswell. The VPTT of hybrid microgels is greater than that of pure microgels. Gawlitza et al. (2013) studied that the VPTT of [Au-p(NIPAM)] hybrid microgels is greater than that of p(NIPAM) microgels. Gorelikov et al. (2004), Kim and Lee (2004, 2006), and many other scientists have reported the same results for Au-microgels. Au nanostructures are also hydrophobic. Therefore, the VPTT of Au nanostructure hybrid microgels can be smaller than that of pure microgels. Khan and Alhoshan (2013) have observed that the VPTT of Au-p(NIPAM-co-AAc) hybrid microgels (31.4°C) was smaller than that of p(NIPAM-co-AAc) microgels (34.6°C) at pH 4. They explained that the hydrophobicity of microgels increases due to the loading of Au nanorods, so the VPTT of hybrid microgels decreases compared to that of pure microgels.
It has been reported that the VPTT of hybrid microgels can be modulated by varying parameters related to microgels and nanostructures. The VPTT of microgels increases with the decrease in the feed content of thermoresponsive monomer. Contreras-Cáceres et al. (2009) have reported that, if Au and BIS content are kept constant, then the VPTT of Au-p(NIPAM) hybrid microgels increases from 36°C to 42°C by decreasing the feed content of NIPAM from 100% to 40%. Lapresta-Fernández et al. (2014) have observed that the VPTT of hybrid microgels decreases by increasing the content of cross-linker tetraethylene glycol dimethacrylate. According to the best of our knowledge, the modulation of the VPTT of negative thermoresponsive Au-microgels by varying the content of Au nanostructures has not been reported in the literature yet. It is possible that the Au content can affect the value of the VPTT of negative temperature-responsive microgels, because Echeverria and Mijangos (2010) have reported that the Au content affects the transition temperature of positive temperature-responsive microgels. However, more research work is needed in this area.
4.1.2 Positive temperature-responsive behavior
Those hybrid microgels that swell at high temperatures and deswell at low temperatures are called positive temperature-responsive microgels. Polymer-polymer interaction breaks away at high temperatures. An increase in temperature favors the formation of hydrogen bonds of water molecules with the polymer network. Therefore, water rushes into microgel particles and they swell. That temperature at which volume phase transition occurs in positive temperature-responsive microgels is termed as the upper critical solution temperature (UCST). Echeverria and Mijangos (2010) have reported such microgels. They synthesized p(AAm-co-AAc) microgels and Au-p(AAm-co-AAc) hybrid microgels. They studied their temperature-responsive behavior. They observed that these pure and hybrid microgels swell with the increase in temperature. They also observed that the UCST of hybrid microgels was greater than that of pure microgels. They observed that the UCST of hybrid microgels increases with the increase in the content of Au. The increase in the UCST is due to the interactions developed between Au nanoparticles and polymeric network of microgels. Therefore, the mobility of polymeric chains decreases with the addition of Au nanoparticles. In this way, the ability of hybrid microgel to swell decreases and the UCST increases with the increase of Au content.
4.2 pH-responsive behavior
The microgels having ionic units inside the network are known as pH-responsive microgels. Hybrid microgels are pH responsive, similar to that of pure microgels, because the fabrication of Au nanostructures does not distort their pH-responsive behavior. Based on the nature of ionic monomer, there are three types of pH-responsive Au-microgels: cationic, anionic, and ampholyte hybrid microgels.
4.2.1 Anionic microgels fabricated with Au nanostructures
The network units having carboxyl groups act as anionic pH-responsive moiety in microgels. Every acid has its specific pKa value. When the pH of the medium is less than the pKa of acidic monomer, then carboxyl groups are present in protonated form (-COOH). Protonated carboxyl groups are less hydrophilic compared to that of carboxylate ions (-COO-). Therefore, protonated carboxyl groups do not develop strong bonds with water molecules. Water molecules squeeze out easily and microgel deswell. When the pH of the medium is greater than the pKa of acidic monomer, then carboxyl groups exists as carboxylate ions. Carboxylate ions are negatively charged. They repel each other and push the polymer network apart. Water molecules rush into the microgel network and the size of microgel increases resultantly. Carboxylate ions develop hydrogen bonding with water molecules. Therefore, carboxylate ions hold water molecules inside the microgel network and maintain microgels in swollen state. The VPT pH of hybrid and pure microgels are almost same. Kim and Lee (2006) studied that the VPT occurred around pH 4.5 in p(NIPAM-co-AAc) microgels and Au-p(NIPAM-co-AAc) hybrid microgels. The pKa of AAc is 4.25, which is very near to VPT pH.
4.2.2 Cationic microgels fabricated with Au nanostructures
Cationic microgels possess amino group (-NH2) as pH-responsive group inside the network. These microgels deswell with the increase in pH. Amino groups are present in the protonated state when the pH of the medium is smaller than its pKa of basic monomer. Protonated amino groups are positively charged, so they repel each other and push the polymer network apart. Thus, water moves into microgel and microgel swells. When the pH of the medium is greater than the pKa of cationic monomer, then amino groups are in neutral state. Electrostatic repulsion among amino groups vanishes and polymer-polymer interactions become strong. Water is expelled out and microgels shrink. Lazim et al. (2012) investigated the pH-responsive behavior of p(NIPAM-co-2-vinyl pyridine) [p(NIPAM-co-2VP)] microgels and Au-p(NIPAM-co-2VP) hybrid microgels. They found that hybrid microgels remain in swollen state between pH 1 and 4. When the pH of the medium has approached the pKa of 2VP (~5), then microgels started deswelling. When the pH of the medium was more than 8, then microgels deswelled completely. Both microgels and hybrid microgels deswell at the same pH values, which means that the presence/absence of Au nanoparticles had no effect on VPT pH.
4.2.3 Ampholyte microgels fabricated with Au nanostructures
Ampholyte microgels are copolymers of cationic and anionic monomers. Therefore, they behave like both kinds of microgels: cationic and anionic. Ampholyte microgels swell two times and deswell three times in the whole pH range (0–14). When the pH of the medium is highly acidic, then these microgels are in deswollen state. When the pH of the medium is less acidic, then microgels are in swollen state due to the protonation of cationic moiety. The pH of the medium increases up to the pKa of cationic moiety and microgel deswells. When the pH of the medium increases above the pKa of cationic moiety, then microgels become deswollen. When the pH of the medium is increased above the pKa of anionic moiety, then microgels again swell up due to the deprotonation of anionic moiety. It means that microgels are present in deswollen state when the pH of the medium is between the pKa of anionic and cationic moieties. Das et al. (2008) have synthesized p(NIPAM-co-AAc-co-vinyl imidazole) [p(NIPAM-co-AAc-co-VI)] ampholyte microgels and studied their pH-responsive behavior. They observed a similar pH-responsive behavior as described above. The loading of Au nanostructures did not affect the pH-responsive behavior of microgels. Therefore, it was considered that Au-p(NIPAM-co-AAc-co-VI) hybrid microgels will show a responsive behavior similar to p(NIPAM-co-AAc-co-VI) microgels.
4.3 Photoresponsive behavior
The photoresponsive behavior is the property of a hybrid microgel to swell and deswell in response to light. Au nanostructures possess SPR band. They may absorb in visible, microwave, or infrared regions depending on the size of nanostructures and environment around nanostructures. When the wavelength of incident radiation approaches the λSPR, then resonance occurs and nanostructures absorb those radiations. Au nanostructures absorb light energy due to SPR and convert it into heat energy through radiationless relaxation process. This heat energy causes VPT in hybrid microgels. Shiotani et al. (2007), Budhlall et al. (2008), and Suzuki et al. (2007) have synthesized hybrid microgels that are responsive to infrared, microwave, and visible radiations, respectively. They used these hybrid microgels in drug delivery, microlensing, and glucose sensing. Photothermal swelling and deswelling is reversible. Scientists have reported that Au-microgels can deswell and swell on many heating and cooling cycles (Budhlall et al. 2008). Au-p(NIPAM-co-acrylamide) hybrid microgels were eight times exposed to microwave radiations for 5 min. The hybrid microgel showed shrinking on exposure to radiation and swelling in the absence of radiation. They observed that the photothermal swelling/deswelling of hybrid microgel was reversible. It was also observed that Au nanoparticles did not coalesce or leak out from microgels during consecutive heating and cooling cycles.
4.4 Glucose-responsive behavior
Glucose-responsive microgels swell and deswell in response to change in glucose concentration. These microgels possess the glucose-responsive moiety as pendant group. When Au nanoparticles or nanorods are incorporated within these microgels, then their glucose sensitivity does not vanish. Hybrid microgels show glucose responsive behavior similar to that of pure microgels. Boronic acid is a glucose-responsive moiety. Acidic carboxyl groups of microgels are coupled with APBA to produce glucose-responsive microgels. When the pH of the medium is increased and reached above the pKa of boronic acid, then boronic acid changes into boronate ions. Boronate ions have high tendency to bind with glucose compared to boronic acid. When boronate ions bind with glucose molecules, then the polymer network is dragged outside due to this new bond formation. Therefore, water molecules rush into hybrid microgels and swelling occurs. The number of bonded glucose molecules increases with the increase in the concentration of glucose. The size of hybrid microgels increases by increasing the concentration of glucose up to a certain limit. When all boronate ions have bonded to glucose molecules, then the size of microgels is not affected by the increasing concentration of glucose anymore. Zhang et al. (2012) have synthesized glucose-responsive poly(N-isoproylacrylamide-co-3-acrylamidophenylboronic acid) [p(NIPAM-co-APBA)] microgels and Au-p(NIPAM-co-APBA) hybrid microgels. They studied their glucose sensitivity by increasing the glucose concentration from 0 to 30 mm. They observed that the size of microgels and hybrid microgels was linearly increased by increasing the glucose concentration from 0 to 10 mm. However, the size of microgels and hybrid microgels are not affected by increasing the glucose concentration from 10 to 30 mm. They concluded that 10 mm is the threshold value after which microgels did not show glucose-responsive behavior. When the concentration of glucose is 10 mm in the medium, then all boronate ions have bonded to glucose, so the size of microgels did not change between 10 and 30 mm glucose concentration. They observed that pure and hybrid microgels show glucose sensitivity between 0 and 10 mm. Therefore, the incorporation of Au nanorods did not affect glucose sensitivity range of microgels. Glucose-responsive hybrid microgels are largely used in insulin delivery devices and glucose sensors due to their glucose-responsive behavior.
5 Optical properties of Au-microgels
Au nanostructures are well-known plasmonic materials. These particles can absorb in the visible to infrared regions depending on the aspect ratio of nanostructures and the nature and refractive index of surrounding medium. The dimensions and distribution of nanostructures are determined by the number and broadness of SPR bands, respectively. Spherical Au nanoparticles possess one SPR band. Au nanorods possess two SPR bands (longitudinal and transverse) (Karg et al. 2007). Longitudinal band is due to the length of nanorod, whereas transverse band is due to the width of nanorod. When Au nanostructures are fabricated in microgels, then the SPR bands of Au nanostructures do not vanish. Hybrid microgels also absorb radiation similar to that of naked Au nanostructures. However, the modulation of SPR bands of nanostructures in hybrid microgels is easier as compared to that of naked nanostructures. The position of SPR band also depends on the distance between nanostructures and the environment around nanostructures (Akamatsu et al. 2009, Karg et al. 2009). The shift in SPR band is observed because microgels change the environment around nanostructures by swelling and deswelling. Water is present in large amount around nanostructures in swollen state. When hybrid microgels deswell with the increase in temperature, then the polymer network is present in the vicinity of nanostructures. It means that the environment around nanostructures changes from polar to nonpolar as easier a result of thermoresponsive deswelling of hybrid microgels. The speed of plasmon is smaller in nonpolar medium compared to that of polar medium. Therefore, the λSPR shifts towards longer wavelength with thermoresponsive deswelling. Rodríguez-Fernández et al. (2011) synthesized Au-p(NIPAM) hybrid microgel and studied the change in its optical properties with thermoresponsive swelling/deswelling. They observed that the longitudinal λSPR of Au nanorods showed red shift with thermoresponsive deswelling only. Contreras-Cáceres et al. (2008) also observed that the λSPR of Au nanoparticles fabricated in p(NIPAM) microgels increases due to temperature-responsive deswelling.
The λSPR also shifts due to the pH-responsive swelling and deswelling of hybrid microgels. Anionic hybrid microgels swell at high pH and deswell at low pH. Anionic groups are in protonated state at low pH, so hybrid microgels deswell. A nonpolar network is present in the vicinity of nanostructures in deswollen state. At high pH, anionic groups get charged and water rushes into microgels. Therefore, in swollen state, polar medium is present in the surrounding of nanostructures. It means that the polarity of environment around nanostructures increases with the increase in pH. Blue shift appears in the λSPR with the increase in pH. Shi et al. (2014) observed that the λSPR of Au-p(NIPAM-co-MAAc) hybrid microgels increased from 514 to 553 nm when the pH of the medium increases from 4.0 to 7.6.
The λSPR of hybrid microgels also shifts due to glucose-responsive swelling and deswelling. The binding of glucose can cause swelling in hybrid microgels having phenylboronic acid groups in their network. Therefore, the medium around nanostructures changes and the λSPR shifts. Zhang et al. (2012) synthesized glucose-responsive Au-p(NIPAM-co-APBA) hybrid microgels. They observed that the λSPR was shifted from 723 to 672 nm when the glucose concentration was changed from 0 to 10 mm. The hydrodynamic radius of hybrid microgels was increased with the increase in glucose concentration. The medium around nanorods become polar. The speed of plasmon is greater in the polar medium than that in the nonpolar medium. That is why the λSPR shifts towards shorter wavelength with the increase in glucose concentration.
The swelling/deswelling of hybrid microgels caused by variation in temperature, pH, and glucose concentration significantly affects the value of the λSPR. This provides the basis of optical detection of glucose as well as the development of pH and temperature sensors. Moreover, photoresponsive drug delivery systems can be designed by the unique combination of optical and stimuli-responsive properties of Au nanostructures and microgels, respectively (Jones and Lyon 2000, Shiotani et al. 2007, Zhang et al. 2012).
The value of λSPR can be kept same in swollen and deswollen state of hybrid microgels by covering the Au nanostructure by metallic shell having no λSPR. Sanchez-Iglesias et al. (2009) have used this approach. They covered Au nanoparticles by platinum (Pt) shell and later covered Pt shell by nickel (Ni) shell. Then, they fabricated polymer on this nanoparticle. The λSPR is not a property of Pt and Ni nanostructures. Therefore, the λSPR of microgels fabricated with Au-Pt-Ni nanoparticles is the same in swollen and deswollen states, because Au is not exposed to environmental conditions. This is the way by which scientists can retain the λSPR at the same position under different conditions of medium.
6 Assembling of microgels fabricated with Au nanostructures
Hybrid microgels can be assembled into an ordered/random manner. Jones et al. (2003) have studied the assembling of microgels fabricated with Au nanoparticles due to photothermal swelling and deswelling. When hybrid microgels are exposed to the radiation of the wavelength λSPR, then Au nanoparticles absorb light energy and convert it into heat energy. Nanoparticles transfer heat energy to microgel and cause deswelling in them. Deswollen hybrid microgel particles came close to each other and arranged into a random/ordered manner. Glassy and crystalline phases are formed from disordered and ordered assembling of microgel particles, respectively. They also studied that illumination time, laser intensity, and wavelength of incident laser affected the crystal/glass assembly of hybrid microgels. They reported that the heating effect is more prominent when the wavelength of incident radiation is resonant with the λSPR. If the wavelength of incident laser is in resonance with the λSPR, then photothermal deswelling occurs quickly and a crystalline phase is formed. If difference between the wavelength of incident laser and the λSPR increases, then the rate of photothermal deswelling decreases. The chances of crystalline phase formation decrease with the decrease in rate of photothermal deswelling. They also observed, if incident wavelength is resonant with the λSPR, then the chances of formation of homogeneous crystalline phase increase with the increase in illumination time and laser intensity. Thus, they optimized the extent of crystalline phase formation of hybrid microgels by changing the above-mentioned parameters.
Kumar et al. (2007) have reported that hybrid microgels can be orderly assembled by tailoring the position of Au nanostructure. They fabricated Au nanorods on the surface of p(NIPAM). Au nanorods were attached from the width side onto the microgel surface. On standing, these hybrid microgels are arranged into hexagonal ordered structures. They confirmed the formation of long-range ordered structures from TEM images. Au nanorods interlocked with each other and assembled the microgels in the form of hexagons. They observed that packing efficiency increases by increasing the loading of Au nanorods on microgels.
The approach of Kumar et al. (2007) towards the assembling of hybrid microgels is totally different from that of Jones et al. (2003). Kumar et al. (2007) assembled hybrid microgels in swollen state, whereas Jones et al. (2003) assembled microgels in deswollen state. Such assembled structures of hybrid microgels can replace expensive liquid crystals and lenses.
7 Characterization of Au-microgels
8 Applications of Au-microgels
Microgels fabricated with Au nanorods have been used in photothermal drug delivery and photothermal therapy fields of biomedicine. Hybrid microgels transfer drug into body by swelling/deswelling of responsive polymeric network. The longitudinal SPR band of Au nanorods lies in the near-infrared range. Therefore, Au nanorods absorb near-infrared radiation and transfer energy to microgels. This energy increases the temperature of microgels; hence, microgels deswell and solvent molecules move out. Near-infrared radiation is not harmful for the human body, because cells of the body do not absorb in this region. Thus, drug loaded within hybrid microgels can be easily transferred to medium on photothermal deswelling. Any carrier of nanorods that fulfills the following criteria can be used for drug delivery. Fortunately, microgels fulfill all the following criteria.
Temperature- and pH-induced swelling/deswelling must take place at physiological conditions (~37°C temperature and ~7.45 pH). p(NIPAM-co-AAc) microgels fulfill this demand (Das et al. 2007).
The swelling ratio of carrier must be large, so the maximum number of drug molecules can be transferred via a small dose of carrier. The swelling ratio of all microgels is very large. Even the swelling ratio of microgels can be controlled by varying cross-linking density. Thus, the extent of release of drug can be controlled using microgels (Das et al. 2007).
The nanorods should remain stable upon reversible swelling and deswelling within carrier. Microgels also fulfill this demand. Nanorods are found to be stable within microgels. They do not aggregate or leak out from microgels upon consecutive swelling and deswelling cycles (Gorelikov et al. 2004, Shiotani et al. 2007).
Gorelikov et al. (2004) loaded Au nanorods into p(NIPAM-co-AAc) microgels and designed a photoresponsive system for drug delivery (Figure 1). They optimized the SPR band of nanorods in the near-infrared range by changing the aspect ratio of nanorods. They found that nanorods of aspect ratio 3 possess SPR band at 804 nm at pH 4. Therefore, they bombarded hybrid microgels with laser of 810 nm wavelength. This photothermal heating induced deswelling in these hybrid microgels and water molecules moved out. If drug-loaded hybrid microgels are implanted into the body and the targeted area of body is bombarded by 810 nm radiation, then drug molecules can also be moved out as a result of photothermal deswelling. Das et al. (2007) and Kawano et al. (2009) have also synthesized such Au-microgels, which showed deswelling upon exposure to near-infrared radiation. Das et al. (2007), Kawano et al. (2009), and Gorelikov et al. (2004) practically did not load any drug into hybrid microgels. They did not study whether hybrid microgels worked after the loading of drug or not. This gap was fulfilled by Shiotani et al. (2007). Shiotani et al. (2007) loaded rhodamine-labeled dextran drug into Au-p(NIPAM) core-shell hybrid microgels. They used near-infrared laser of power 750 mW and wavelength 1064 nm. They observed that the drug was really moved out of hybrid microgels due to photothermal deswelling. They confirmed it using TEM images and dynamic light scattering (DLS) measurements. Rhodamine is a fluorescent drug, so they confirmed the position of the drug in the system from fluorescence spectroscopic images. It is clear from these images that drug molecules reside within hybrid microgels in swollen state while they move out in deswollen state. They had also taken images after consecutive heating and cooling cycles. They observed that, once the drug had been delivered, then the drug molecules did not move back into microgels on cooling. Therefore, their work gives confirmation to the research of Gorelikov et al. (2004), Das et al. (2007), and Kawano et al. (2009).
Au-microgels absorb radiation and transfer their energy to medium in the form of heat. In this way, they increase the temperature of the medium. The viability of tumor cells is affected by temperature. Hybrid microgels have been used to kill tumor cells by photothermal therapy. Zhang et al. (2014) have used Au-p(NIPAM-co-AAc) hybrid microgels for the in vivo treatment of breast cancer 4T1 cells by photothermal therapy. Initially, they optimized the size of hybrid microgels in swollen and deswollen states, so that microgels could easily travel through tumor vessels. They also studied that cell viability was not affected by the presence of p(NIPAM-co-AAc) microgels. Then, they implanted hybrid microgels into tumor cells and then irradiated that body part with laser having wavelength comparable to the longitudinal λSPR of nanorod and observed tumor weight loss. They also heated the affected body part by dipping mice in hot water and observed tumor weight loss. They observed that weight loss in tumor cells by photothermal therapy is greater than that by thermal therapy. Doxorubicin drug is used for the chemical treatment of 4T1 cells. They compared tumor weight loss by doxorubicin-loaded hybrid microgels and naked doxorubicin. They observed that tumor weight loss in both cases is almost same. However, they observed that hybrid microgels delivered drug into nucleus of cells, whereas naked doxorubicin could not approach the nucleus of cells. Thus, hybrid microgels effectively transferred drug into cells. They also compared the photochemical and thermochemical treatment of tumor cells by drug-loaded hybrid microgels. They observed that the tumor inhibition rate by photochemical treatment was faster than that by thermochemical treatment. In this way, they practically studied photothermal therapy and drug delivery by hybrid microgels.
8.2.1 Microgel-based sensing
APBA-coupled hybrid microgels are well-known glucose-responsive materials. Zhang et al. (2012) used APBA to design a glucose sensor that can detect glucose at low concentrations. They coupled APBA with p(NIPAM-co-AAc) microgels to prepare p(NIPAM-co-APBA) microgels. Then, they mixed microgel dispersion with Au nanorod dispersion and synthesized hybrid microgels. They mixed both dispersions at different pH. They optimized the conditions to such limit at which nanorods show the maximum shift in the λSPR in response to a very small change in the concentration of glucose. They observed that synthesized hybrid microgels swell in the presence of glucose. Due to swelling, the λSPR of nanorods shifted and the signal is recorded due to the shifting of the λSPR. They observed that the λSPR decreases from 723 to 672 nm when the concentration of glucose was increased from 0 to 10 mm at pH 9 and temperature at 30°C. When the concentration of glucose was increased above 10 mm, then no change in the λSPR and the size of microgel were observed. It means that this sensor could measure the concentration of dilute glucose solutions only. Zhang et al. (2012) did not mention that synthesized hybrid microgels can be used for the delivery of insulin within the body. Hybrid microgels swell in response to glucose concentration, so insulin can be easily leaked out from microgels in swollen state. Insulin decreases the level of glucose in human body. Insulin is not produced by the body of diabetic patients, so insulin injections are given to them. If insulin-loaded hybrid microgels are injected into their bodies, then there is no need to check their blood glucose level from time to time. The APBA of microgels automatically checks the blood glucose level and releases insulin according to the demand of the body. A pictorial diagram of glucose concentration-mediated drug release is shown in Figure 2.
8.2.2 Nanostructure-based sensing
Analyte molecules can be nonfluorescent or fluorescent. Both types of analytes interact differently with nanostructures. Nonfluorescent analytes give surface-enhanced Raman scattering (SERS) in deswollen hybrid microgels only. They do not give SERS in swollen hybrid microgels. On the contrary, fluorescent analytes give surface-enhanced resonance Raman scattering (SERRS) in deswollen hybrid microgels and surface-enhanced fluorescence (SEF) in swollen hybrid microgels. SERS, SERRS, and SEF are ultrasensitive analytical spectroscopies. If one molecule of analyte binds to Au nanostructure, then that can be easily detected with these spectroscopic techniques. In this way, a quantitative analysis is done using Au-microgels.
When nonfluorescent analyte molecules bind to the surface of Au nanostructure, then Au nanostructures show SERS. It is mandatory for SERS that analyte binds with Au nanostructures. Hybrid microgels have ensured the binding of analyte with Au nanostructures. Analyte molecules move into the microgel network in swollen state. When microgels deswell, then analyte molecules do not move out of microgels, but they get trapped within microgels. Therefore, analyte molecules come very close to Au nanostructures and get attached. Hence, the peaks in SERS are observed. Álvarez-Puebla et al. (2009) synthesized Au-p(NIPAM) core-shell hybrid microgels and used them for the ultrasensing of 1-naphthalene thiol (NAT). They put hybrid microgels in NAT solution and heated them to 4°C and 60°C. They scanned SERS spectra at 4°C and 60°C. They observed that the sample at 4°C showed no SERS peaks, whereas the sample at 60°C showed SERS peaks. NAT molecules moved into the microgel network at 4°C. When the temperature was increased to 60°C, then NAT molecules get trapped within microgel and came close to the Au surface. NAT molecules have a thiol group that has high affinity for Au. NAT molecules were chemisorbed on the surface of Au nanoparticles due to the Au-S bond formation. When NAT molecules had adsorbed, then peaks appeared in SERS spectra. When the sample heated to 60°C was cooled to 4°C, then the peaks in SERS spectra did not vanish. This confirmed that NAT molecules had chemisorbed on nanoparticle surface and could not be removed. They also observed the same changes in SERS spectra during the cooling/heating cycle of 60°C→4°C→60°C. If the number of adsorbed molecules is increased, then the height of SERS peaks increases and this technique can work for single-molecule detection. Similarly, Dong et al. (2014) detected 1-naphthol in samples using Au-p(NIPAM) hybrid microgels. Manikas et al. (2014) also detected adenine using microgels fabricated with Au nanoparticles.
In the case of fluorescent analytes, SEF and SERRS spectra are observed. When fluorescent molecules are irradiated with their λmax, then they get excited. When the excited florescent analyte molecules are in the close vicinity of Au nanostructures, then the SPR of Au nanostructure interacts with analyte and peaks in SEF spectra results. When the excited fluorescent analyte binds with Au nanostructure, then the peaks in SERRS spectra appear. Álvarez-Puebla et al. (2009) studied the ultrasensing of Nile blue A dye (NBD) by Au-p(NIPAM) core-shell hybrid microgels. They studied the change in SEF and SERRS spectra of Au-p(NIPAM) hybrid microgels in the presence of NBD during 4°C→60°C→4°C and 60°C→4°C→60°C cooling/heating cycles. At 4°C, hybrid microgels were in swollen state and excited NBD molecules were present in the vicinity of Au nanoparticles. Plasmon of Au nanoparticles interacts with NBD molecules and peaks appeared in SEF spectra. The peaks in SEF spectra indicated the presence of NBD molecules within hybrid microgels. When hybrid microgels were deswelled by heating to 60°C, then NBD molecules were adsorbed on the surface of Au nanoparticles and the peaks in SERRS spectra appeared. When this system was cooled to 4°C again, then the peaks in SERRS spectra disappeared. The disappearance of peaks indicated that NBD molecules were physically adsorbed on the surface of Au nanoparticles. NBD had amino groups, which had less affinity for Au compared to that of NAT. That is why physical adsorption was shown by NBD and chemical adsorption was shown by NAT. The same peaks in SERRS and SEF spectra were observed in swollen and deswollen states during the 60°C→4°C→60°C cooling/heating cycle. Thus, Au-p(NIPAM) hybrid microgels can sense the presence of analyte in very dilute solutions. All types of analytes can be analyzed by the SERS spectroscopic technique.
Au-microgels are largely used in the catalysis of different chemical reactions. A pictorial diagram of the catalytic applications of various Au-microgels are shown in Figure 3. Hybrid microgels have the following advantageous properties that facilitate the process of catalysis.
The high swelling ratio of hybrid microgels facilitates the diffusion of reactants towards the surface of nanoparticles.
Hybrid microgels are responsive to various stimuli, so they help to tune the catalytic activity of nanoparticles by various stimuli, such as temperature and pH of the medium.
Hybrid microgels can be easily separated from the reaction mixture by centrifugation or ultrafiltration. Therefore, microgel-based catalyst can be used again and again.
The catalytic activity of hybrid microgels can also be tuned by varying structural parameters of microgels, such as cross-linking density.
Microgels resist the leaching of nanostructures. Therefore, hybrid microgel-based catalysts do not lose their catalytic activity and can be reused.
Shi et al. (2013) used Au-p(NIPAM-co-AET) hybrid microgels as catalyst for the reduction of 4-NP in aqueous medium. They studied the effect of temperature on the value of apparent rate constant (kapp) of reduction. NIPAM is a thermoresponsive monomer. Therefore, they observed a nonlinear dependence of ln kapp on 1/T (Figure 4). Initially, the value of ln kapp increases by increasing the temperature from 30°C to 36°C due to the Arrhenius behavior of reaction. Then, the value of ln kapp decreases by increasing the temperature from 36°C to 40°C. This is due to the deswelling of hybrid microgels. Due to deswelling, the approach of reactants towards the surface of catalyst becomes difficult and the value of ln kapp decreases. Then, the value of ln kapp again increases by increasing the temperature from 40°C to 52°C. This is again due to Arrhenius behavior. Agrawal et al. (2013) studied the effect of the surface area of catalyst on kapp of 4-NP reduction using Au-poly(N-vinylcaprolactam)-poly(aceto acetoxy ethyl methacrylate)-poly(AAc) [Au-p(VCL)-p(AAEM)-p-(AAc)] core-shell-shell hybrid microgels as catalyst. They prepared three different hybrid microgels in which the size of Au nanoparticles was same but the number of nanoparticles was different. They observed that the value of kapp is maximum for the sample having the highest number of nanoparticles among all samples. Actually, the surface area for catalysis increases by increasing the number of nanoparticles; hence, the value of kapp increases by increasing the surface area. They also observed a very small decrease in the catalytic activity of hybrid microgels when they were reused again and again. Wu et al. (2012) studied the catalytic reduction of hydrophilic 4-NP and hydrophobic NB reduction within the same medium at same time using Au-p(NIPAM) yolk-shell hybrid microgels. They observed that the value of kapp of the reduction of 4-NP is greater than that of NB before the VPTT. They also observed that the value of kapp of the reduction of 4-NP is smaller than that of NB after the VPTT. Actually, NIPAM is hydrophilic before the VPTT and hydrophobic after the VPTT. Also, 4-NP is comparatively more polar compared to that of NB. Like dissolves like, so 4-NP rapidly diffuse through the p(NIPAM) network before the VPTT and NB rapidly diffuse through polymer network after the VPTT. They also observed nonlinear dependence of ln kapp on 1/T due to the responsive nature of hybrid microgels.
The reduction of potassium hexacyanoferrate (III) (K3[Fe(CN)6]) was studied by Carregal-Romero et al. (2010) using Au-p(NIPAM) core-shell hybrid microgels as catalyst. They studied the effect of catalyst dosage, temperature and cross-linking density of polymer network on the catalytic activity of hybrid microgels. They observed that the value of kapp linearly increases by increasing the catalyst dosage. They also observed that the catalytic activity of swollen hybrid microgels is different from that of deswollen hybrid microgels. The difference between the catalytic activity of hybrid microgels in swollen and deswollen states depends on their swelling ratio because nanoparticles of exterior portion are only available in the deswollen state. The swelling ratio of hybrid microgels decreases by increasing the cross-linking density. It means that densely cross-linked hybrid microgels are less temperature responsive compared to that of loosely cross-linked hybrid microgels. Therefore, the catalytic activity of densely cross-linked microgels was not significantly affected by temperature and the catalytic activity of loosely cross-linked microgels was significantly affected by temperature.
Jia et al. (2015) compared the catalytic activity of α-cyclodextrin-modified Au-p(VCL) hybrid microgels for the reduction of 4-NP and 2,6-dimethyl-4-nitrophenol (2-DMNP). They noticed that the catalytic activity of Au-p(VCL) hybrid microgels was greater for 4-NP in comparison to 2-DMNP. They explained that α-cyclodextrin formed strong complex with 4-NP and weak complex with 2-DMNP. That is why the difference in catalytic activity is observed due to the difference in substrate-catalyst affinity.
This discussion reveals that Au-microgels are applicable for the catalysis of organic and inorganic reactions. Scientists proved that the catalytic activity is dependent on catalyst dosage, size of nanoparticles, structure of microgels, and temperature. However, they did not calculate the energy, entropy, and enthalpy of activation of catalytic process in the swollen and deswollen states of hybrid microgels. From Figure 4, it is clear that the slope of plot in swollen and deswollen states are different from each other. It means that activation parameters are different in swollen and deswollen states, so they must be reported. Moreover, the actual mechanism of catalysis has not been discussed in detail yet. NIPAM-based microgels are soluble in organic solvents at high temperatures, but Au nanoparticle-based hybrid microgels have not been used as catalyst in nonaqueous medium. Therefore, some gaps are still present in the study of catalytic applications of Au-microgels, and more work is necessary in this area to explain the hidden facts in the field of catalysis by Au-microgels.
Au-microgels have the ability to diffract light rays. Photothermal swelling and deswelling occur in them. Deswollen microgel particles can assemble into glassy and crystalline phases as discussed in Section 6. The distance between nanostructures decreases due to deswelling in microgels. The sieves of microgels are of nanosize, so the distance among nanostructures approaches the diffraction limit in deswollen microgels. Therefore, deswollen hybrid microgels can act as diffraction grating. When visible radiation falls on microgel-based grating, then radiation diffracts into rings. Thus, light rays are diffracted into a specific direction using microgel-based grating. This property of hybrid microgels was used by Jones et al. (2003) to prepare photothermally patterned microlens. Jones et al. (2003) used Au-p(NIPAM) hybrid microgels as a microlens to magnify the fine details of images. When hybrid microgels are irradiated with a wavelength of 532 nm, then hybrid microgels deswelled rapidly and converted into crystalline ordered phase. They placed an object on one side of hybrid microgels and a visible radiation source on the other side of hybrid microgels. When radiation falls on crystalline phase, then they diffract towards object. They illuminated the object and magnified its fine details. Words that were not clearly visible by hand lens become visible by microlens due to diffraction. They explained that diffraction occurred due to the reflection of light rays from the microgel-air interface (A) and mirror-air interface (A′). d is the distance between microgel-air interface and mirror-air interface. A path difference of λ/2 is induced between ray A and A′ (Figure 5). These rays constructively interfere at this path difference; hence, illumination and magnification of image occurred. Thus, hybrid microgel-based crystalline phase can be used as an efficient microlens in place of expensive quartz crystals.
Microgels help in the coating of nanostructures in the form of thin film on different substrates. Initially, hybrid microgel particles are dispersed on water in a trough. A substrate, such as glass slide, is present in trough in tilted orientation (i.e. making 45° angle with the base of trough). Then, water is drain out from trough, so that water level starts decreasing. Microgel particles also move down due to the downward movement of water. Microgel particles are smoothly adsorbed on substrate due to the downward movement of water. Then, the pressure is applied for strong adherence of hybrid microgels on the substrate. Then, the substrate is annealed at high temperature or exposed to plasma, so that the microgel network gets decomposed. Nanostructures will be naked and coated on substrate. Yolk-shell and core-shell hybrid microgels are most suitable for this purpose because one nanostructure is present per microgel particle. Therefore, the chances of heterogeneous coating can be reduced. Vogel et al. (2012) have practically coated glass slide with Au nanoparticles with the help of Au-p(NIPAM) yolk-shell structures. They studied that the distance between nanostructures are not affected by the magnitude of applied pressure. However, the magnitude of applied pressure affected the degree of order in coating. Long-range ordered coating was obtained at high magnitude of applied pressure. Clara-Rahola et al. (2014) have studied the effect of temperature on the coating of Au nanoparticles. As Rh of Au-p(NIPAM) core-shell hybrid microgels decreases with the increase in temperature, the distance between nanoparticles in microgel film decreases with the increase in temperature. That is why they coated hybrid microgels on glass slide at different temperatures. As a result, they observed that the number of nanoparticles per unit area of substrate increased with the increase in temperature. Nanostructure-coated substrates have found applications in SERS ultrasensitive analysis and photonics (Vogel et al. 2012). According to the best of our knowledge, no one has practically used such nanostructure-coated substrates for any application. Hence, more work is needed in this area to extend it towards the applied direction.
9 Future directions
The unique combination of the optical properties of Au nanostructures and the smart behavior of polymer microgels in the form of Au-microgels is increasing its demand day by day. These hybrid microgels can open new gates of applications in the future. Here, some lines are highlighted on which work can be done. A variety of Au-microgels have been reported. However, yolk-shell hybrid microgels having Au nanorods have not been reported yet. Yolk-shell hybrid microgels have a large space for storing drugs. Therefore, the incorporation of Au nanorods within a yolk-shell structure can deliver a large volume of drug in the future. Many parameters that can affect the VPTT have been studied. However, the effect of Au content on UCST of negative thermoresponsive microgels has not been studied yet. Ampholyte hybrid microgels swell in acidic as well in basic media. No application of these microgels has been reported. These microgels can be used for catalysis, sensing, and photonics. Au-microgels have been used as catalyst in aqueous media only. NIPAM microgels are soluble in nonaqueous media at high temperatures, so they can be used for the catalysis in nonaqueous media. Microgels fabricated with Au-Pt-Ni nanostructure have not been used for any application practically. As this nanostructure is paramagnetic and infrared absorbing, it can be used for photomagnetic applications in the future.
The classification, synthesis, properties, and responsive behavior of Au-microgels have been reviewed here. Yolk-shell, core-shell, core-shell-shell, hollow rings, and microspheres are various types of Au-microgels that have been reported in the literature. Hybrid microgels swell and deswell in response to stimuli, such as pH, temperature, glucose, and light radiation. Au-microgels have a wide range of applications such as glucose sensing, drug delivery, analyte analysis, and microlensing. The glucose-sensitive behavior of Au-microgels is reported here as an efficient method for monitoring blood glucose level as well as targeted delivery of insulin in diabetic patients. Au-microgels are used for the accurate analysis of analytes because they can detect the presence of one molecule of analyte in a sample. Microlensing and optical properties are reported as an effective method for the illumination as well as magnification of images.
Funding: University of the Punjab, Lahore, (Grant/Award Number: D/473/Est.I).
Agrawal G, Schürings MP, van Rijn P, Pich A. Formation of catalytically active gold-polymer microgel hybrids via a controlled in situ reductive process. J Mater Chem A 2013; 1: 13244–13251.CrossrefGoogle Scholar
Akamatsu K, Shimada M, Tsuruoka T, Nawafune H, Fujii S, Nakamura Y. Synthesis of pH-responsive nanocomposite microgels with size-controlled gold nanoparticles from ion-doped, lightly cross-linked poly (vinylpyridine). Langmuir 2009; 26: 1254–1259.CrossrefGoogle Scholar
Álvarez-Puebla RA, Contreras-Cáceres R, Pastoriza-Santos I, Pérez-Juste J, Liz-Marzán LM. Au@ pNIPAM colloids as molecular traps for surface–enhanced, spectroscopic, ultra–sensitive analysis. Angew Chem Int Ed 2009; 48: 138–143.CrossrefGoogle Scholar
Bradley M, Garcia-Risueno BS. Symmetric and asymmetric adsorption of pH-responsive gold nanoparticles onto microgel particles and dispersion characterisation. J Colloid Interface Sci 2011; 355: 321–327.CrossrefGoogle Scholar
Carregal-Romero S, Pérez-Juste J, Hervés P, Liz-Marzán LM, Mulvaney P. Colloidal gold-catalyzed reduction of ferrocyanate (III) by borohydride ions: a model system for redox catalysis. Langmuir 2009; 26: 1271–1277.CrossrefGoogle Scholar
Clara-Rahola J, Contreras-Caceres R, Sierra-Martin B, Maldonado-Valdivia A, Hund M, Fery A, Hellweg T, Fernandez-Barbero A. Structure and plasmon coupling of gold-poly(N-isopropylacrylamide) core-shell microgel arrays with thermally controlled interparticle gap. Colloids Surf A 2014; 463: 18–27.CrossrefGoogle Scholar
Contreras-Cáceres R, Sánchez-Iglesias A, Karg M, Pastoriza-Santos I, Pérez-Juste J, Pacifico J, Hellweg T, Fernández-Barbero A, Liz–Marzán LM. Encapsulation and growth of gold nanoparticles in thermoresponsive microgels. Adv Mater 2008; 20: 1666–1670.CrossrefGoogle Scholar
Contreras-Cáceres R, Pacifico J, Pastoriza-Santos I, Pérez-Juste J, Fernández-Barbero A, Liz-Marzán LM. Au@ pNIPAM thermosensitive nanostructures: control over shell cross–linking, overall dimensions, and core growth. Adv Funct Mater 2009; 19: 3070–3076.CrossrefGoogle Scholar
Daniel MC, Astruc D. Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. Chem Rev 2004; 104: 293–346.CrossrefGoogle Scholar
Das M, Sanson N, Fava D, Kumacheva E. Microgels loaded with gold nanorods: photothermally triggered volume transitions under physiological conditions. Langmuir 2007; 23: 196–201.CrossrefGoogle Scholar
Dong X, Zou X, Liu X, Lu P, Yang J, Lin D, Zhang L, Zha L. Temperature-tunable plasmonic property and SERS activity of the monodisperse thermo-responsive composite microgels with core-shell structure based on gold nanorod as core. Colloids Surf A 2014; 452: 46–50.CrossrefGoogle Scholar
Dulle M, Jaber S, Rosenfeldt S, Radulescu A, Förster S, Mulvaney P, Karg M. Plasmonic gold-poly (N-isopropylacrylamide) core-shell colloids with homogeneous density profiles: a small angle scattering study. Phys Chem Chem Phys 2015; 17: 1354–1367.CrossrefGoogle Scholar
Echeverria C, Mijangos C. Effect of gold nanoparticles on the thermosensitivity, morphology, and optical properties of poly(acrylamide-acrylic acid) microgels. Macromol Rapid Commun 2010; 31: 54–58.CrossrefGoogle Scholar
Gawlitza K, Turner ST, Polzer F, Wellert S, Karg M, Mulvaney P, von Klitzing R. Interaction of gold nanoparticles with thermoresponsive microgels: influence of the cross-linker density on optical properties. Phys Chem Chem Phys 2013; 15: 15623–15631.CrossrefGoogle Scholar
Jain T, Tehrani-Bagha AR, Shekhar H, Crawford R, Johnson E, Nørgaard K, Holmberg K, Erhart P, Moth-Poulsen K. Anisotropic growth of gold nanoparticles using cationic Gemini surfactants: effects of structure variations in head and tail groups. J Mater Chem C 2014; 2: 994–1003.Google Scholar
Jia H, Schmitz D, Ott A, Pich A, Lu Y. Cyclodextrin modified microgels as “nanoreactor” for the generation of Au nanoparticles with enhanced catalytic activity. J Mater Chem A 2015; 3: 6187–6195.CrossrefGoogle Scholar
Karg M, Lu Y, Carboo-Argibay E, Pastoriza-Santos I, Peerez-Juste J, Liz-Marzaan LM, Hellweg T. Multiresponsive hybrid colloids based on gold nanorods and poly (NIPAM-co-allylacetic acid) microgels: temperature-and pH-tunable plasmon resonance. Langmuir 2009; 25: 3163–3167.CrossrefGoogle Scholar
Kawano T, Niidome Y, Mori T, Katayama Y, Niidome T. PNIPAM gel-coated gold nanorods for targeted delivery responding to a near-infrared laser. Bioconjugate Chem 2009; 20: 209–212.CrossrefGoogle Scholar
Khan A, Alhoshan M. Preparation and characterization of pH-responsive and thermoresponsive hybrid microgel particles with gold nanorods. J Polym Sci Pt A Polym Chem 2013; 51: 39–46.CrossrefGoogle Scholar
Lange H, Juárez BH, Carl A, Richter M, Bastús NG, Weller H, Thomsen C, von Klitzing R, Knorr A. Tunable plasmon coupling in distance-controlled gold nanoparticles. Langmuir 2012; 28: 8862–8866.CrossrefGoogle Scholar
Lapresta-Fernández A, García-García JM, París R, Huertas-Roa R, Salinas-Castillo A, de la Llana SA, Huertas-Pérez JF, Guarrotxena N, Capitán-Vallvey LF, Quijada-Garrido I. Thermoresponsive gold polymer nanohybrids with a tunable cross-linked MEO2MA polymer shell. Part Part Syst Char 2014; 31: 1183–1191.CrossrefGoogle Scholar
Lazim A, Julian E, Melanie B. Incorporation of gold nanoparticles into pH responsive mixed microgel systems. Mediterr J Chem 2012; 1: 259–272.Google Scholar
Manikas AC, Romeo G, Papa A, Netti PA. Highly efficient surface-enhanced Raman scattering substrate formulation by self-assembled gold nanoparticles physisorbed on poly(N-isopropylacrylamide) thermoresponsive hydrogels. Langmuir 2014; 30: 3869–3875.CrossrefGoogle Scholar
Pich A, Karak A, Lu Y, Ghosh AK, Adler H-JP. Hybrid microgels containing gold nanoparticles. e-Polymers 2006; 6: 226–241.Google Scholar
Rodríguez-Fernández J, Fedoruk M, Hrelescu C, Lutich AA, Feldmann J. Triggering the volume phase transition of core-shell Au nanorod-microgel nanocomposites with light. Nanotechnology 2011; 22: 245708–245716.CrossrefGoogle Scholar
Sakai T, Horiuchi Y, Alexandridis P, Okada T, Mishima S. Block copolymer-mediated synthesis of gold nanoparticles in aqueous solutions: segment effect on gold ion reduction, stabilization, and particle morphology. J Colloid Interface Sci 2013; 394: 124–131.CrossrefGoogle Scholar
Sanchez-Iglesias A, Grzelczak M, Rodríguez-González B, Guardia-Giros P, Pastoriza-Santos I, Pérez-Juste J, Prato M, Liz-Marzán LM. Synthesis of multifunctional composite microgels via in situ Ni growth on pNIPAM-coated Au nanoparticles. ACS Nano 2009; 3: 3184–3190.CrossrefGoogle Scholar
Shi S, Zhang L, Wang T, Wang Q, Gao Y, Wang N. Poly (N-isopropylacrylamide)-Au hybrid microgels: synthesis, characterization, thermally tunable optical and catalytic properties. Soft Matter 2013; 9: 10966–10970.CrossrefGoogle Scholar
Shi S, Wang Q, Wang T, Ren S, Gao Y, Wang N. Thermo-, pH-, and light-responsive poly(N-isopropylacrylamide-co-methacrylic acid)-Au hybrid microgels prepared by the in situ reduction method based on Au-thiol chemistry. J Phys Chem B 2014; 118: 7177–7186.CrossrefGoogle Scholar
Shiotani A, Mori T, Niidome T, Niidome Y, Katayama Y. Stable incorporation of gold nanorods into N-isopropylacrylamide hydrogels and their rapid shrinkage induced by near-infrared laser irradiation. Langmuir 2007; 23: 4012–4018.CrossrefGoogle Scholar
Suzuki D, Nagase Y, Kureha T, Sato T. Internal structures of thermosensitive hybrid microgels investigated by means of small-angle X-ray scattering. J Phys Chem B 2014; 118: 2194–2204.Google Scholar
Vogel N, Fernández-López C, Pérez-Juste J, Liz-Marzán LM, Landfester K, Weiss CK. Ordered arrays of gold nanostructures from interfacially assembled Au@ PNIPAM hybrid nanoparticles. Langmuir 2012; 28: 8985–8993.CrossrefGoogle Scholar
Wen S, Li K, Cai H, Chen Q, Shen M, Huang Y, Peng C, Hou W, Zhu M, Zhang G. Multifunctional dendrimer-entrapped gold nanoparticles for dual mode CT/MR imaging applications. Biomaterials 2013; 34: 1570–1580.CrossrefGoogle Scholar
Wu S, Dzubiella J, Kaiser J, Drechsler M, Guo X, Ballauff M, Lu Y. Thermosensitive Au-PNIPA yolk-shell nanoparticles with tunable selectivity for catalysis. Angew Chem Int Ed 2012; 51: 2229–2233.CrossrefGoogle Scholar
Xiao C, Wu Q, Chang A, Peng Y, Xu W, Wu W. Responsive Au@ polymer hybrid microgels for the simultaneous modulation and monitoring of Au-catalyzed chemical reaction. J Mater Chem A 2014; 2: 9514–9523.CrossrefGoogle Scholar
Zhang Y, Liu K, Guan Y, Zhang Y. Assembling of gold nanorods on P (NIPAM-AAPBA) microgels: a large shift in the plasmon band and colorimetric glucose sensing. RSC Adv 2012; 2: 4768–4776.CrossrefGoogle Scholar
Zhang Z, Wang J, Nie X, Wen T, Ji Y, Wu X, Zhao Y, Chen C. Near infrared laser-induced targeted cancer therapy using thermoresponsive polymer encapsulated gold nanorods. J Am Chem Soc 2014; 136: 7317–7326.CrossrefGoogle Scholar
About the article
Zahoor H. Farooqi
Zahoor H. Farooqi obtained his PhD in chemistry in 2013 from the Qauid-i-Azam University (Islamabad, Pakistan). He has worked with Professor Dr. Shuiqin Zhou under the Pakistan-US Science and Technology Cooperative Program 2007. He joined the Institute of Chemistry, University of the Punjab (Lahore, Pakistan), as a lecturer in 2008. He is currently working as an assistant professor of physical chemistry at the same institute.
Shanza Rauf Khan
Shanza Rauf Khan obtained her MSc degree in chemistry in 2012 from the Institute of Chemistry, University of the Punjab (Lahore, Pakistan). She stood top in the MSc exam and was awarded a gold medal. In 2015, she completed her MPhil degree in physical chemistry under the supervision of Dr. Zahoor H. Farooqi. She has been working as a lecturer at the Centre for Undergraduate Studies, University of the Punjab (Lahore, Pakistan), since 2013.
Robina Begum obtained both her MSc in chemistry (2009) and her MPhil in chemistry (2011) from the Institute of Chemistry, University of the Punjab (Lahore, Pakistan). She is working as a lecturer of chemistry at the Centre for Undergraduate Studies, University of the Punjab (Lahore, Pakistan).
Aysha Ijaz obtained her BS in chemistry in 2013 from the Government College University (Faisalabad, Pakistan). She stood top in the BS exam and was awarded a gold medal. She has completed her MPhil degree under the supervision of Dr. Zahoor H. Farooqi.
Published Online: 2015-12-11
Published in Print: 2016-02-01