Abstract: A non-invasive method to measure metal nanoparticle concentrations in bulk tissue is provided. A simple diagnostic assay to detect nanoparticle concentration in bulk tissue has been developed herein. One such provided method comprises: applying diffuse optical spectroscopy to a tissue having nanoparticles disposed therein; and applying an inverse algorithm to the light reflected from the nanoparticles. Another such method comprises: exposing tissue that comprises nanoparticles to a light source; collecting light from the tissue using an optical fiber probe; and measuring the concentration of nanoparticles in the tissue. A system is provided comprising: a tissue comprising nanoparticles; a light source arranged to illuminate a portion of the tissue; an optical fiber probe to collect light reflected from the tissue; and a spectrometer to measure the light reflected from the nanoparticles and operably connected to a computer having one or more processors and a memory.