Protein-Templated Core/Shell Au Nanostructures for Intracellular Reactive Oxygen Species Detection by SERS

Core/shell gold “raspberry” nanostructures capable of multiple therapeutic functionalities were synthesized using a template composed of monodispersed anionic protein (bovine serum albumin) nanoparticles coated with a cationic biopolymer (poly-l-lysine). The nanostructures exhibited high photothermal conversion efficiency when exposed to a near-infrared (NIR) laser, which led to significant cellular inhibition of A549 human lung cancer cells due to intracellular hyperthermia. The raspberry structures also provided hot spots for surface-enhanced Raman scattering (SERS) ratiometric sensing of intracellular reactive oxygen species (ROS) when modified with the Raman reporter molecule 4-aminothiophenol (4-ATP). ROS was detected in A549 lung cancer cells upon photothermal heating of internalized nanostructures, enabling a possible mechanism for feedback on therapeutic efficacy. This was confirmed by adding the antioxidant N-acetylcysteine (NAC) and using a complementary fluorescence technique, which showed that the amount of detectable intracellular ROS decreased. These safe-by-design gold raspberry nanostructures could be promising for simultaneous therapeutic applications and monitoring therapeutic efficacy.