Gold nanocages

Optical fluorescence imaging is increasingly used to monitor biological functions of specific targets (1-3). However, the intrinsic fluorescence of biomolecules poses a problem when fluorophores that absorb visible light (350–700 nm) are used. Near-infrared (NIR) fluorescence (700–1,000 nm) detection avoids the background fluorescence interference of natural biomolecules, providing a high contrast between target and background tissues. NIR fluorophores have a wider dynamic range and minimal background as a result of reduced scattering compared with visible fluorescence detection. They also have high sensitivity, resulting from low infrared background, and high extinction coefficients, which provide high quantum yields. The NIR region is also compatible with solid-state optical components, such as diode lasers and silicon detectors. NIR fluorescence imaging is becoming a noninvasive alternative to radionuclide imaging in small animals (4, 5). Photoacoustic imaging (PAI) is an emerging hybrid biomedical imaging modality based on the photoacoustic effect. In PAI, non-ionizing optical pulses are delivered into biological tissues. Some of the delivered energy is absorbed and converted into heat, leading to transient thermoelastic expansion and thus ultrasonic emission. The generated ultrasonic waves are then detected by ultrasonic transducers to form images. It is known that optical absorption is closely associated with physiological properties, such as hemoglobin concentration and oxygen saturation. As a result, the magnitude of the ultrasonic emission (i.e., the photoacoustic signal), which is proportional to the local energy deposition, reveals physiologically specific optical absorption contrast and tissue structures. However, exogenous NIR contrast agents are necessary to overcome the intrinsic low tissue- and hemoglobin- absorption and scattering of tissue. On the other hand, these small molecules exhibit fast clearance, small optical absorption cross section, and non-targeted specificity. Therefore, there is a need for contrast agents with long blood circulation and targeted specificity. Gold (Au) nanoparticles have been studied as molecular imaging agents because of their bright NIR fluorescence emission around 700–900 nm and low toxicity (6, 7). They can be tuned to emit in a range of wavelengths by changing their sizes, shapes, and composition, thus providing broad excitation profiles and high absorption coefficients. They can be coated and capped with hydrophilic materials for additional conjugation with biomolecules, such as peptides, antibodies, nucleic acids, and small organic compounds for and studies. Au nanoparticles have been approved by the United States Food and Drug Administration for treatment of patients with rheumatoid arthritis. Au nanoparticles have been studied as contrast agents in X-ray/computed tomography, NIR optical coherence tomography, PAI, and photoacoustic tomography (PAT) (8). NIR Au nanocages are biocompatible, have low toxicity, and are tunable to strong NIR absorption (9). They have an outer edge of ~50 nm and an inner edge of ~42 nm, with a wall thickness of ~4 nm. Yang et al. (10) performed PAT of the cerebral cortex of rats with poly(ethylene glycol)-coated Au nanocages (PEG-AuNCs) as the optical contrast agent. The investigators observed an enhanced optical contrast in the vasculature in the cerebral cortex. Song et al. (11) demonstrated the use of Au nanocages as a PAI probe for detection of sentinel lymph node (SLN) of rats.