Gold Nanocage Assemblies for Selective Second Harmonic Generation Imaging of Cancer Cell

Second harmonic generation (SHG) imaging using near infrared laser light is the key to improving penetration depths, leading to biological understanding. Unfortunately, currently SHG imaging techniques have limited capability due to the poor signal‐to‐noise ratio, resulting from the low SHG efficiency of available dyes. Targeted tumor imaging over nontargeted tissues is also a challenge that needs to be overcome. Driven by this need, in this study, the development of two‐photon SHG imaging of live cancer cell lines selectively by enhancement of the nonlinear optical response of gold nanocage assemblies is reported. Experimental results show that two‐photon scattering intensity can be increased by few orders of magnitude by just developing nanoparticle self‐assembly. Theoretical modeling indicates that the field enhancement values for the nanocage assemblies can explain, in part, the enhanced nonlinear optical properties. Our experimental data also show that A9 RNA aptamer conjugated gold nanocage assemblies can be used for targeted SHG imaging of the LNCaP prostate cancer cell line. Experimental results with the HaCaT normal skin cell lines show that bioconjugated nanocage‐based assemblies demonstrate SHG imaging that is highly selective and will be able to distinguish targeted cancer cell lines from other nontargeted cell types. After optimization, this reported SHG imaging assay could have considerable application for biology.