Department of Neurosurgery, MacKay Memorial Hospital , Taipei, Taiwan 104.
Department of Bio-Industrial Mechatronics Engineering, National Taiwan University , Taipei, Taiwan 10617.
ACS Appl Mater Interfaces. 2017 Feb 1;9(4):3873-3884. doi: 10.1021/acsami.6b12591. Epub 2017 Jan 20.
This paper describes the synthesis of near-infrared (NIR)-absorbing gold nanoframes (GNFs) and a systematic study comparing their physiological stability and biocompatibility with those of hollow Au-Ag nanoshells (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 %, 4-fold lower than that of the GNSs. These GNFs displayed an attractive photothermal conversion ability and 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.
本文描述了近红外（NIR）吸收金纳米框架（GNFs）的合成，并系统地比较了它们与空心 Au-Ag 纳米壳（GNSs）的生理稳定性和生物相容性，后者由于其在 NIR 区域的局域表面等离子体共振（LSPR）而被广泛用作生物医学应用中的光热剂。GNFs 通过三步合成：电置换、Au 沉积和 Ag 脱合金，以银纳米球（SNP）为起始材料。GNFs 的形态和光学性质取决于 Au 涂层的厚度和 Ag 脱合金的程度。最佳的 GNF 表现出由几个厚边缘组成的坚固球形骨架，但保留了在 NIR 区域的独特 LSPR 吸收——即使骨架内的 Ag 含量仅为 10wt%，比 GNSs 低 4 倍。这些 GNFs 表现出吸引人的光热转换能力和良好的光热稳定性，并能通过光诱导加热有效地杀死 4T1 癌细胞。此外，GNFs 在生物介质（如盐水、血清）中孵育后保留其形态和光学性质，而 GNSs 在相同条件下不稳定，因为壳内的大量银迅速溶解。此外，GNFs 对正常细胞（如 NIH-3T3 和肝细胞；两种细胞的细胞活力：>90%）具有良好的生物相容性，而 GNSs 表现出显著的剂量依赖性细胞毒性（如肝细胞在 1.14 nM 时的细胞活力：约 11%），同时诱导活性氧的产生。最后，GNFs 在体内小鼠模型中表现出良好的生物相容性和生物安全性；相比之下，GNSs 的积累导致肝损伤和炎症。我们的结果表明，GNFs 具有作为体内应用（包括癌症检测和联合治疗）中稳定、生物相容的 NIR 光吸收剂的巨大潜力。
