The near-infrared photoluminescence from non-covalently dispersed single-walled carbon nanotubes (SWCNT) is optimally suited to probe distinct classes of biological environments. At the single cell level, DNA-nanotubes enter live cells via endocytosis at 37°C and remain within the endosomal pathway, with their final localization exclusively in the lysosomes. By carefully screening DNA sequences for their sensitivity to lysosomal components accessible to the carbon nanotube, we present a platform to assay changes in the lysosomal environment via a resulting modulation of nanotube fluorescence.