Bioinspired protein corona strategy enhanced biocompatibility of Ag-Hybrid hollow Au nanoshells for surface-enhanced Raman scattering imaging and on-demand activation tumor-phototherapy.

Abstract Silver-based hybrid nanoprobes for surface-enhanced Raman scattering (SERS) imaging show their tremendous potential for precise biological detection and mediated phototherapy. However, the severe toxicity induced by Ag to normal mammalian cells hinders its further application. Herein, we presented a versatile bioinspired protein corona strategy through assembling bovine serum albumin (BSA) protected Raman tag DTTC-conjugated Ag-hybrid hollow Au nanoshells (hollow AgAu-DTTC-BSA), which their silver ion release and reactive oxygen species (ROS) generation are significantly suppressed, enabling no damage to normal cells and tissues, but can be reactivated on-demand under laser-irradiation at the tumor site. These nanoshells could also produce strong localized surface plasmon resonance for efficient-stable photothermal effect and enhanced SERS activity under laser irradiation, approved by both theoretical and experimental calculations. Furthermore, the biocompatible hollow AgAu-DTTC-BSA could detect both primary tumor tissues and tiny liver metastases (~0.18 mm) in orthotopic/subcutaneous CT26 colon tumor-bearing mice models. We also demonstrate their excellent therapeutic efficacy for colorectal solid neoplasms by accurate SERS imaging-guided photothermal therapy, simultaneously assisted with toxic Ag ion and ROS. These results suggest that hollow AgAu-DTTC-BSA is promising imaging assisted photothermal agents for solid tumor theranostics and enhancing the potential of Ag-based nanoparticles for practical treatment.