Schematic diagrams showing the structure, preparation, and pH-responsive behavior of smart SERS nanoparticles. (a) Molecular structure of pH-induced conformational changes of a thiolated block copolymer consisting of a pH-responsive ploymethacrylic acid (PMAA) block (MW 3000), an amphiphilic polyethylene glycol (PEG) block (MW 5000), and a terminal lipoic acid (LA) anchoring group. (b) Preparation of dye-encoded gold nanoparticle with SERS and stimuli-responsive properties. (c) Nanoparticle aggregation induced by polymer conformational changes, leading to plasmonic coupling and SERS. Each gold particle (60 nm) was tagged with ∼1,000 reporter molecules (such as organic dyes) and was encapsulated with ∼104 LA-PEG-PMAA copolymer molecules.