Near-IR-Absorbing Gold Nanoframes with Enhanced\nPhysiological Stability and Improved Biocompatibility for In Vivo\nBiomedical Applications

This\npaper describes the synthesis of near-infrared (NIR)-absorbing gold\nnanoframes (GNFs) and a systematic study comparing their physiological\nstability and biocompatibility with those of hollow Au–Ag nanoshells\n(GNSs), which have been used widely as photothermal agents in biomedical\napplications because of their localized surface plasmon resonance\n(LSPR) in the NIR region. The GNFs were synthesized in three steps:\ngalvanic replacement, Au deposition, and Ag dealloying, using silver\nnanospheres (SNP) as the starting material. The morphology and optical\nproperties of the GNFs were dependent on the thickness of the Au coating\nlayer and the degree of Ag dealloying. The optimal GNF exhibited a\nrobust spherical skeleton composed of a few thick rims, but preserved\nthe distinctive LSPR absorbance in the NIR regioneven when\nthe Ag content within the skeleton was only 10 wt %, 4-fold lower\nthan that of the GNSs. These GNFs displayed an attractive photothermal\nconversion ability and great photothermal stability, and could efficiently\nkill 4T1 cancer cells through light-induced heating. Moreover, the\nGNFs preserved their morphology and optical properties after incubation\nin biological media (e.g., saline, serum), whereas the GNSs were unstable\nunder the same conditions because of rapid dissolution of the considerable\nsilver content with the shell. Furthermore, the GNFs had good biocompatibility\nwith normal cells (e.g., NIH-3T3 and hepatocytes; cell viability for\nboth cells: >90%), whereas the GNSs exhibited significant dose-dependent\ncytotoxicity (e.g., cell viability for hepatocytes at 1.14 nM: ca.\n11%), accompanied by the induction of reactive oxygen species. Finally,\nthe GNFs displayed good biocompatibility and biosafety in an in vivo\nmouse model; in contrast, the accumulation of GNSs caused liver injury\nand inflammation. Our results suggest that GNFs have great potential\nto serve as stable, biocompatible NIR-light absorbers for in vivo\napplications, including cancer detection and combination therapy.