Improving biomedical imaging with gold nanocages

To improve early cancer detection, researchers are developing in vivo biomedical imaging techniques with the resolution to distinguish between healthy and malignant tissue.^1,2 Yet these techniques could still be improved with contrast enhancement agents.³ Gold nanostructures are promising for optical imaging because they can absorb and scatter light at specific wavelengths.⁴ This phenomenon, called localized surface plasmon resonance (LSPR), can improve contrast by enhancing or damping the optical signals characteristic of certain types of tissue.

To be useful in biomedical imaging, the LSPR must be tuned in the near-infrared (NIR) range, where light attenuation by blood and soft tissue is minimal. This requirement cannot be achieved with simple gold colloids. To overcome this challenge, researchers prepared gold nanoshells (composite particles with a metallic shell and dielectric core) and nanorods that can be tuned into the NIR.⁴ Because they are difficult to predictably prepare, however, we shifted our focus to hollow, porous structures called nanocages.⁵

Figure 1. (a) Scanning electron micrograph of gold nanocages. (Inset: transmission electron micrograph, scale bar = 25nm.) (b) (top) Vials containing the structures prepared with different volumes of 0.1mM HAuCl₄ solution and (bottom) the corresponding absorbance spectra.^6,8

The LSPR of the nanocages can be tuned with ease and precision.⁶ We use a simple replacement reaction:

to generate and deposit gold onto the surfaces of silver nanocubes, while simultaneously removing silver from the interior. Figure 1(a) shows transmission electron and scanning electron micrographs of the particles. As these cubic structures transform first into boxes, then into porous cages, the LSPR shifts from the visible to the NIR range. Figure 1(b) shows different volumes of hydrogen tetrachloroaurate gold precursor (HAuCl₄ solution) and the corresponding absorption spectra. The final position depends on the initial amounts of precursor, so tuning to a specific wavelength is easy and controllable.

The nanocages have light absorption cross-sections almost five orders of magnitude greater than those of organic dyes. Additionally, they are relatively non-toxic and their surfaces can easily be decorated with biomolecules. These properties make them ideal candidates for nanomedicine.⁷

In collaboration with Lihong Wang's group at Washington University in St. Louis, we recently demonstrated the nanocages' utility as contrast enhancement agents for photoacoustic tomography (PAT).⁸ PAT is a hybrid imaging modality that integrates optical and ultrasonic techniques. It measures ultrasonic waves produced when light absorption causes the thermoelastic expansion of tissue. We imaged the cerebral cortex of a rat before and after the administration of the particles.⁸ The LSPR of the nanocages was tuned to ∼820nm, which overlaps with both the biologically transparent window and the wavelength of light used in PAT. Figure 2 shows PAT images before and after their administration. Administration of the nanocages enhanced optical absorption of the vasculature by up to 81%.

Figure 2. PAT of a rat's cerebral cortex before and after gold nanocage administration.⁸ The contrast agent increased vascular optical absorption by 81%.

This simple demonstration illustrates the enhancement gold nanocages can bring to optical imaging by selectively enhancing light absorption in vivo. Our next steps will focus on targeting nanocages to cancer cells in vivo using optical coherence tomography and two photon luminescence imaging.