A seven-step approach was developed to synthesize poly(acrylic acid-b-2-hydroxyethyl methacrylate) [P(AA-b-HEMA)]-based temperature- and pH-sensitive hollow nanospheres. Silica nanoparticles were used as primary cores that could be etched with an aqueous hydrofluoric acid (HF) solution. A surface-attached atom transfer radical polymerization initiator was converted to a reversible addition fragmentation chain transfer (RAFT) agent, and AA and HEMA were polymerized via "grafting from" RAFT polymerization. The PAA block was cross-linked partially via an esterification reaction with -COOH groups with 1,4-butanediol, and hollow nanospheres were obtained by etching silica cores with an aqueous HF solution. These hollow nanospheres exhibited dual pH-sensitive and thermosensitive properties as measured by the hydrodynamic diameter at different values of pH (3-12) and temperature (25-55 degrees C) at different concentrations (1 and 5 mg/mL). Results showed that this behavior could be changed at different concentrations; therefore, at low contents, the particles show one lower critical solution temperature (LCST), while at higher contents, two LCSTs are observed.