Wang and coworkers have used this technique to image the distribution of Au-nanoshells circulating in the vasculature of a rat brain by achieving a gradual enhancement of the NIR optical absorption in the brain vessels [115]. These Au-nanocages enhanced the contrast between blood and the surrounding

tissues by up to 81%, allowing a more detailed image of vascular structures at greater depths. Additionally, these nanocages were shown to be better suited for in vivo applications, specially due to their more compact size (<50nm find more compared to >100nm for Au-nanoshells) and larger optical absorption cross sections when compared to Au-nanoshells. Gold-nanorods show Inhibitors,research,lifescience,medical the maximum of the plasmon Inhibitors,research,lifescience,medical resonance tuned further into the NIR that allowed Motamedi et al. to develop a contrast agent for a laser optoacoustic imaging system for in vivo detection of gold nanorods and to enhance the diagnostic power of optoacoustic imaging [116]. Song et al. proposed a noninvasive in vivo spectroscopic photoacoustic sentinel lymph node mapping using gold nanorods as

lymph node tracers in a rat model [117]. Also, noble metal NP probes can be used for in situ diagnostics of cancer. For example, NP-based NIR probes can overcome several limitations of conventional NIR organic dyes, such as poor hydrophilicity and photostability, low Inhibitors,research,lifescience,medical quantum yield and detection Inhibitors,research,lifescience,medical sensitivity, insufficient stability in biological systems, and weak multiplexing capability. Additionally, the high

scattering properties of these NPs can enhance contrast of imaging systems based on microscopy, such as dark-field or dual-photon luminescence microscopy. Zhang et al. developed fluorescent metal nanoshells as molecular imaging agents to detect single microRNA (miRNA) molecules in lung cancer cells [47]. These metal nanoshells were composed of silica spheres with encapsulated Ru(bpy)32+ complexes as core and thin silver layers as shell. Inhibitors,research,lifescience,medical The silver shell allowed to enhance emission intensity up to 6-fold and photostability by 2-fold, as well as to achieve longer lifetime emission signals that overcome cellular autofluorescence interference. Loo et al. demonstrated the use of NIR scattering Au-nanoshells as a contrast agent in dark-field microscopy however to target antihuman epidermal growth factor receptor 2 (HER2), a clinically significant breast cancer molecular marker [72]. These Au-nanoshells were also used by Bickford et al. for imaging live HER2-overexpressing cancer cells using two-photon microscopy [118]. Surface-enhanced Raman scattering (SERS) using Au- or AgNPs with an attached reporter species with a Raman signature can be explored to highlight cellular structures and provide molecular structural information on the cellular environment in live cells [119, 120].