Light-active nanomaterials, which convert photon energy efficiently into chemical, electronic, or thermal energy, have been used widely with many practical applications in fields ranging from energy to health. Among common light sources, near-infrared (NIR) light is particularly suitable for excitation of light-responsive nanomaterials in the human body because it can penetrate into deep biological tissues, the result of low absorption by water and blood as well as weak scattering from soft tissue in the NIR region. Recently, an increasing number of studies have been conducted on hollow Au-Ag nanoshells (GNSs) comprising a thin alloyed shell and a hollow interior. GNSs can transfer NIR photon energy efficiently to generate local heat causing hyperthermia and triggering drug release or to produce cytotoxic ROS to kill cancer cells in a form of photodynamic therapy. However, the residual silver may result in the GNSs displaying instability and toxicity, especially in biological media.
Herein, we reported the synthesis of NIR–absorbing gold nanoframes (GNFs) and a systematic study comparing their physiological stability and biocompatibility with those of GNSs, which have been used widely as photothermal agents in biomedical applications because of their localized surface plasmon resonance (LSPR) in the NIR region. The GNFs were synthesized in three steps: galvanic replacement, Au deposition, and Ag dealloying, using silver nanospheres (SNP) as the starting material. The morphology and optical properties of the GNFs were dependent on the thickness of the Au coating layer and the degree of Ag dealloying. The optimal GNF exhibited a robust spherical skeleton composed of a few thick rims, but preserved the distinctive LSPR absorbance in the NIR region—even when the Ag content within the skeleton was only 10 wt%, fourfold lower than that of the GNSs. These GNFs displayed an attractive photothermal conversion ability, great photothermal stability, and could efficiently kill 4T1 cancer cells through light-induced heating. Moreover, the GNFs preserved their morphology and optical properties after incubation in biological media (e.g., saline, serum), whereas the GNSs were unstable under the same conditions because of rapid dissolution of the considerable silver content with the shell. Furthermore, the GNFs had good biocompatibility with normal cells (e.g., NIH-3T3 and hepatocytes; cell viability for both cells: >90%), whereas the GNSs exhibited significant dose-dependent cytotoxicity (e.g., cell viability for hepatocytes at 1.14 nM: ca. 11%), accompanied by the induction of reactive oxygen species. Finally, the GNFs displayed good biocompatibility and biosafety in an in vivo mouse model; in contrast, the accumulation of GNSs caused liver injury and inflammation. Our results suggest that GNFs have great potential to serve as stable, biocompatible NIR-light absorbers for in vivo applications, including cancer detection and combination therapy.