Tumors constitute many different cell types including epithelial cells, endothelial cells, fibroblasts, and macrophages. Endothelial cells form a barrier for nanomaterial delivery to tumors and other disease sites. Dysregulation in endothelial cells is associated in many pathological conditions including cancers. Nanoscale probes that can localize to specific endothelial cells may facilitate the understanding of disease processes. Single-walled carbon nanotubes (SWCNTs) are ideal tools for bio-imaging due to their non-bleaching photoluminescence in the near infrared region and molecular sensing capabilities that stem from environmental sensitivity of their optical bandgap. We non-covalently ‘cloaked’ carbon nanotubes with helical polycarbodiimide polymers to develop water soluble, biocompatible optical nanoprobes. We found that the use of different polycarbodiimide substituents modulated the surface chemistry of the carbon nanotubes to regulate uptake by epithelial and endothelial cells.