Seeded Growth of Cu_2–xSe Nanocrystals and Their Size-Dependent Phototherapeutic Effect

Doped semiconductors supporting localized surface plasmon resonances, such as nonstoichiometric copper chalcogenides Cu2–xSe, have been intensively researched for their potential applications in photoacoustic imaging and photothermal therapy. For these self-doped nanoparticles, their physicochemical attributes such as size and surface chemistry will not only affect their cellular uptake and biodistribution but also influence their own optical properties. Thus, optimization of the physicochemical properties is crucial for their nanobio-applications. Through a seeded growth approach, aqueous phase synthesis of monodisperse Cu2–xSe with various sizes has been developed for the first time. Taking three different sized Cu2–xSe NPs (35, 65, and 105 nm in diameter) as examples, their size-dependent optical cross-section, photothermal property, and cellular cytotoxicity have been investigated, and the 65 nm one displays the largest optical cross-section at 21.57 L g–1 cm–1 and best photothermal property per unit mass. In addition, Cu2–xSe exhibits a size-dependent reactive oxygen species generation effect that is inversely proportional to their diameters. Finally, on the basis of optical property and cytotoxicity optimizations, the photothermal cancer cell ablation ability and potential use of Cu2–xSe NPs as photoacoustic contrast enhancing agent has been demonstrated in vivo.