Biofunctionalization of Large Gold Nanorods Realizes Ultrahigh-Sensitivity Optical Imaging Agents

Gold nanorods (GNRs, ∼ 50 × 15 nm) have been used ubiquitously in biomedicine for their optical properties, and many methods of GNR biofunctionalization have been described. Recently, the synthesis of larger-than-usual GNRs (LGNRs, ∼ 100 × 30 nm) has been demonstrated. However, LGNRs have not been biofunctionalized and therefore remain absent from biomedical literature to date. Here we report the successful biofunctionalization of LGNRs, which produces highly stable particles that exhibit a narrow spectral peak (FWHM ∼100 nm). We further demonstrated that functionalized LGNRs can be used as highly sensitive scattering contrast agents by detecting individual LGNRs in clear liquids. Owing to their increased optical cross sections, we found that LGNRs exhibited up to 32-fold greater backscattering than conventional GNRs. We leveraged these enhanced optical properties to detect LGNRs in the vasculature of live tumor-bearing mice. With LGNR contrast enhancement, we were able to visualize tumor blood vessels at depths that were otherwise undetectable. We expect that the particles reported herein will enable immediate sensitivity improvements in a wide array of biomedical imaging and sensing techniques that rely on conventional GNRs.