Optical Characteristics and Tumor Imaging Capabilities of Near Infrared Dyes in Free and Nano-Encapsulated Formulations Comprised of Viral Capsids

Near infrared (NIR) fluorescent molecules and nanosized structures can serve as potential optical probes for image-guided removal of small tumor nodules (≥ 1 mm diameter). Although indocyanine green (ICG) remains as the only FDA-approved NIR dye, other organic dyes are under extensive development for enhanced imaging capabilities. One such dye is BrCy106-NHS where bromine is substituted for aromatic structures in cyanine dyes. Herein, we investigate the absorption and fluorescence characteristics of ICG and BrCy106-NHS, and quantitatively assess their tumor imaging capabilities in free (non-encapsulated) and a nano-encapsulated form that utilizes the capsid protein (CP) from genome-depleted plant-infecting brome mosaic virus as the encapsulating shell. We refer to these nanoconstructs as optical viral ghosts (OVGs). For example, when fabricated at CP to dye concentration ratio of 200, value of the spectrally integrated fluorescence emission for BrCy106-NHS-doped OVGs is ∼60 times higher than that of ICG-doped OVGs. Our analysis of homogenized mice intraperitoneal tumors indicate that the averaged total fluorescence emission associated with the use of BrCy106-NHS-doped can be at least about 44 times greater than that of ICG-doped OVGs. Our results suggest that OVGs containing BrCy106-NHS may potentially serve as effective optical probes for tumor imaging.