Peptide-Directed Hierarchical Mineralized Silver Nanocages for Anti-Tumor Photothermal Therapy

The size and morphology of metals determine their plasmon resonances. How to elegantly tune their architectures to obtain optical properties as required (e.g., strong absorption in the near infrared (NIR) wavelengths) is a bottleneck for phototherapy. Inspired by biomineralization, we develop a simple but robust strategy to fabricate silver nanocages (Ag NCs) based on peptide-directed mineralization of silver. The Ag NCs are organic-inorganic hybrids with octreotide (OCT) templated decoration of Ag shells that are composed of Ag NPs. This hierarchical organization makes Ag NPs get together in close proximity, which facilitates ultrastrong plasmonic coupling to shift the resonant excitation from the visible (420 nm) to the NIR region (810 nm). In addition, the surface plasmon resonance peak of the Ag NCs in the NIR region can be subtly tuned by varying the volume of added silver nitrate (AgNO3) to control the size and morphology of mineralized Ag NCs. The Ag NCs have a light-to-heat conversion efficiency of 46.1%, which is to our knowledge the highest among Ag-based photothermal agents (PTAs). The Ag NCs can selectively induce death of cancer cells in vitro under NIR irradiation at 808 nm and show improved cytocompatibility for normal cells relative to pure Ag NPs. Following intratumor injection into uterine cervix cancer cells (U14) tumor-bearing mice, Ag NCs exert remarkable antitumor performance with tumor killing efficacy up to 82.7% and good biocompatibility in photothermal therapy, suggesting their potential application to work as photothermal nanomedicine for cancer therapy.