# Polymer@gold Nanoparticles Prepared via RAFT Polymerization for Opto-Biodetection
## 4 Au NPs in Opto-Biodetection and Beyond
Unlike the nanocomposites dispersed in pure water, using a NaCl aqueous solution, the optical properties of the colloid are more sensitive to the increase of temperature leading to a red-shift and absorbance decrease in the LSPR band. This effect is the combination of ionic screening of citrate ions at the NPs surfaces and a salting out effect on PNiPAM chains, which lead to dehydration and consequently an increase of hydrophobic interactions [84; 145]. Furthermore, it was found that free PNiPAM in solution promotes the aggregation of PNiPAM/Au nanostructures when the temperature increases, because it works as a cross-linking agent [146; 147]. More recently, [PERSON] et al. have shown a co-operative aggregation behavior using PNiPAM@Au NPs with different cloud point. This parameter was tuned by controlling the MW of PNiPAM chains and the Au NP size [148]. In another thermoresponsive Au nanocomposite based on PNiPAM, with different MW, a fluorophore was used in order to prepare a biosensing platform based on fluorescence quenching to detect six distinct proteins. Depending on the nature of the proteins (MW and isoelectric point--pl), different interactions with the nanostructures were observed by monitoring the photoluminescence emission spectra [83]. PEG-based polymers are also known to have thermosensitivity, and [PERSON] et al. [149] have shown that the LCST can be tuned (from 15 to 90 \({}^{\circ}\)C) by adjusting the ratio of the monomers, oligoethyleneglycol acrylate (OEG-A) and di(ethylene glycol) ethyl ether acrylate (DEG-A), during the RAFT polymerization. Likewise, the poly(OEG-A-_co_-DEG-A)/Au NPs have shown thermoresponsiveness but also protein antifouling properties. Later, a similar study, was performed by using the methacrylate group in these monomers, because the hydrophilicity of the backbone is slightly different and has influence in the LCST. The authors have explored the impact of using statistical or diblock copolymers in the thermal response [87; 150]. Moreover, homo and statistical copolymers prepared by RAFT polymerization, using \(N\)-vinylpyrrolidone and \(N\)-vinylcaprolactone, were grafted to Au NPs and presented temperature-responsive behavior in which the sensitivity increases with NaCl, in the range from 25 to 60 \({}^{\circ}\)C [151]. Other authors go further by producing polymer/Au nanocomposites with dual properties, pH- and temperature-sensitivity. For example, Au NPs were generated in the presence of poly(2-dimethylaminoethyl methacrylate) three-arm star polymers and the resulting hybrid nanostructure showed different LCST values (35 and 45 \({}^{\circ}\)C) for pH 10.5 and 8.4, respectively, as demonstrated by dynamic light scattering (DLS) measurements. Both pH values are above the corresponding p\(K_{\mathrm{a}}\), where hydrophobic interactions take place with an increase of temperature [152]. Also using polymers based on NiPAM, the pH and temperature responsiveness were explored for PNiPAM/Au nanocomposites at pH below the p\(K_{\mathrm{a}}\). In these conditions, by increasing the temperature above the LCST, the nanocomposites migrate to an organic phase (chloroform), due to the increase of hydrophobic interactions, and this behavior was shown to be reversible [153]. More recently, some works have reported applications of RAFT-polymer/Au nanostructures which are sensitive to pH and/or temperature and that are not limited to biodetection. As already mentioned, the \"smart\" nanomaterials cited above are promising platforms to be used in drug delivery systems for example in cancer therapy. Because cancer cells exhibit a microenvironment where the pH is slightly acidic, this can trigger the release of the drug by using a pH-sensitive polymer. On the other hand, by using thermal sensitive polymers, the drug release can be promoted by local heating [154; 155]. For example, [PERSON] et al. [153] polymerized methacrylic acid (MAA) via RAFT polymerization and after reducing the RAFT end group, the thiolated PMAA was grafted to the Au NPs surfaces (\(d\sim 50\) nm).