Protein/Polymer‐Based Dual‐Responsive Gold Nanoparticles with pH‐Dependent Thermal Sensitivity

Abstract

This article presents the synthesis and physicochemical behavior of dual‐responsive plasmonic nanoparticles with reversible optical properties based on protein‐coated gold nanoparticles grafted with thermosensitive polymer brushes by means of surface‐initiated atom transfer radical polymerization (SI‐ATRP) that exhibit pH‐dependent thermo‐responsive behavior. Spherical gold NPs of two different sizes (15 nm and 60 nm) and with different stabilizing agents (citrate and cetyltrimethylammonium bromide (CTAB), respectively) were first capped with bovine serum albumin (BSA). The resulting BSA‐capped NPs (Au@BSA NPs) exhibited not only extremely high colloidal stability under physiological conditions, but also a reversible U‐shaped pH‐responsive behavior, similar to pure BSA. The ϵ‐amine of the L‐lysine in the protein coating was then used to covalently bind an ATRP‐initiator, allowing for the SI‐ATRP of thermosensitive polymer brushes of oligo(ethylene glycol) methacrylates with an LCST of 42 °C in pure water and around 37 °C under physiological conditions. Such protein coated nanoparticles grafted with thermosensitive polymers exhibit a smart pH‐dependent thermosensitive behavior.

Coating matters: the influence of coating materials on the optical properties of gold nanoparticles

“…Chanana et al have reported that gold nanoparticles coated with insulin [153] and BSA [143] exhibit not only reversible pH responsive behavior, but also high colloidal stability due to covalent bonding of proteins to gold nanoparticles through the thiol/disulfi de groups from the cystein residues ( Figure 6 ). Especially the BSA coated gold nanoparticles were shown to display bidirectional pH-sensitivity, where the particles aggregated reversibly at pH = pI BSA (pI BSA ∼ 4.6 -4.9) [143] , but upon increasing or decreasing the pH away from the pI, the particles disaggregated again completely as indicated by the LSPR shift back to its original position. Such stimuli-responsive changes are usually reversible, thus providing access to switchable optical properties.…”

Recent progress on colloidal metal nanoparticles as signal enhancers in nanosensing

“…As the stability and aggregation of (bio)polymer-capped NPs are highly sensitive toward external stimuli, due to the significant structural modifications that such macromolecules register under tiny changes of the (bio)chemical environment [40], a high number of reports have been devoted to LSPR-based nanosensing of parameters such as pH [41], heavy metals [42], and temperature [43], using NPs in colloidal solutions. In an elegant approach, Chanana and co-workers have designed dual-responsive NPs coated by proteins and grafted with thermosensitive polymer brushes that present pH-and thermoresponsive behavior [41].…”

“…In an elegant approach, Chanana and co-workers have designed dual-responsive NPs coated by proteins and grafted with thermosensitive polymer brushes that present pH-and thermoresponsive behavior [41]. Such preparation led to AuNPs with lower critical solution temperatures of 42°C in pure water and around 37°C under physiological conditions, which were followed by LSPR coupling.…”

Physicochemical Properties of Protein‐Coated Gold Nanoparticles in Biological Fluids and Cells before and after Proteolytic Digestion

“…[8] For the synthesis of the fluorescently labeled NPs (Au@protein-F), two different synthetic routes comprising either one or two synthetic steps were used (Figure 1 a). In the one-step synthesis (route a), a commercially available fluorescently labeled protein, ovalbumin labeled with BODIPY FL (45 kDa, Ova-DQ; BODIPY FL = 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pro-pionic acid), was used to coat the Au NPs, whereas in the twostep synthetic method (route b), the fluorescent dye tetramethylrhodamine isothiocyanate (TRITC) was covalently bonded to the presynthesized Au@protein NPs (Au@insulin and Au@BSA) through standard amine-coupling reactions (see the Supporting Information for more details).…”

“…On the other hand, the interior of lysosomes is known to be acidic, usually around pH 4-5. Since the Au@protein NPs are highly pH-sensitive and agglomerate exactly in the pH range of 4-5 (owing to the pI value of the coating proteins), [8] we assumed that the NPs would agglomerate inside lysosomes. Besides their low pH value, lysosomes contain proteolytic enzymes, which, as already shown, can degrade the protein coating.…”