UC San Diego

Marking of colon tumors for surgery is normally done using India ink, but it cannot be imaged below the tissue surface and there is evidence of serious complications such as abscess, intestinal perforation and inconsistency of injection. A novel infrared marker was developed using FDA approved indocyanine green (ICG) dye and ultrathin hollow silica nanoshells. Using a positively charged amine linker, ICG was non-covalently bound to the shell surface. This non-covalent attachment was shown to be stable under biological conditions. For ultra-thin wall 100 nm diameter silica shells, a bimodal ICG layer of < 3 nm was formed. Conversely, for thicker walls on 2 μm diameter silica shells, the ICG layer was only bound to the outer surface and was 6 nm thick. In vitro testing of fluorescent emission showed the particles with the thinner coating were considerably more efficient, consistent with self-quenching in the thicker ICG coatings due to formation of energy traps. Ex vivo testing showed that ICG bound to the 100 nm hollow silica shells was visible under 1.5 cm of tissue. In vivo experiments demonstrated the ability of ICG bound to 100 nm silica shells to mark tumors accurately with no diffusion in tissue and remain visible for over 12 days.