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A "smart" core@shell composite nanoparticle (NP) having dual-response mechanisms (i.e., temperature and light) was synthesized, and its efficacy in the loading and release of small molecules was explored. These core@shell NPs are composed of an optically active gold nanoshell (GNS) core and a mesoporous ( m -) silica layer ( m -SiO 2 ). The GNS@ m -SiO 2 nanoparticles are further encapsulated within a thermo-responsive poly(N-isopropylacrylamide-co-acrylic acid) hydrogel (PNIPAM-co-AA). The multi-responsive composite NPs were designed to create thermally and optically modulated drug-delivery vehicles with a m -SiO 2 layer providing additional non-collapsible space for drug storage. The influence of the m -SiO 2 layer on the efficacy of loading and release of methylene blue, which serves as a model for a small-molecule therapeutic drug, was evaluated. The "smart" core@shell composite NPs having a m -SiO 2 layer demonstrated an improved capacity to load and release small molecules compared to the corresponding NPs with no m -SiO 2 shell. Additionally, an efficient response by the composite NPs was successfully induced by the thermal energy generated from the gold nanoshell core upon exposure to near infrared (NIR) stimulation.

Hydrogel-Encapsulated Mesoporous Silica-Coated Gold Nanoshells for Smart Drug Delivery