Surface Modification of Gold Nanorods (GNRDs) Using Double Thermo-Responsive Block Copolymers: Evaluation of Self-Assembly and Stability of Nanohybrids

A series of copolymers containing a thermo-responsive biocompatible first block of poly[di(ethylene glycol) methyl ether methacrylate)-<i>co</i>-(oligo(ethylene glycol) methyl ether methacrylate], P(DEGMA-<i>co</i>-OEGMA) were chain-extended to incorporate either poly(<i>N</i>-isopropylacrylamide), PNIPAAm or poly(<i>N</i>-isopropylacrylamide-<i>co</i>-butyl acrylate), P(NIPAAm-co-BA) as second thermo-responsive block using reversible addition-fragmentation chain transfer (RAFT) polymerization. P(DEGMA-<i>co</i>-OEGMA)-<i>b</i>-PNIPAAm copolymers showed two response temperatures at 33 and 43 °C in an aqueous solution forming stable aggregates at 37 °C. In contrast, P(DEGMA-<i>co</i>-OEGMA)-<i>b</i>-P(NIPAAm-<i>co</i>-BA) copolymers showed aggregation below room temperature due to the shift in response temperature provoked by the presence of hydrophobic butyl acrylate (BA) units, and shrinkage upon heating up to body temperature, while maintaining the second response temperature above 40 °C. The terminal trithiocarbonate group of the block copolymers was modified to a thiol functionality and used to stabilize gold nanorods (GNRDs) via the "grafting to" approach. The Localized Surface Plasmon Resonance (LSPR) absorption band of GNRDs with an aspect ratio of 3.9 (length/diameter) was located at 820 nm after surface grafting with block copolymers showing a hydrodynamic diameter of 160 nm at 37 °C. On the other hand, the stability of the P(DEGMA-<i>co</i>-OEGMA)-<i>b</i>-PNIPAAm@GNRDs and P(DEGMA-<i>co</i>-OEGMA)-<i>b</i>-P(NIPAAm-<i>co</i>-BA)@GNRDs nanohybrids was monitored for 8 days; where the LSPR absorption band did not shift or show any broadening. Aqueous dispersed nanohybrids were irradiated with a near-infrared laser (300 mW), where the temperature of the surroundings increased 16 °C after 16 min, where conditions for no precipitation were determined. These tailored temperature-responsive nanohybrids represent interesting candidates to develop drug nanocarriers for photo-thermal therapies.