InGaP QDs overcoated with several monolayers of ZnS are covalently bound to chitosan to address the challenges of developing highly biologically stable and fluorescent nanoparticle probes for deep-tissue imaging. Transmission electron microscopy images reveal that the average diameter of these luminescent nanoparticles is approximately 29 nm, and they contain multiple InGaP@ZnS QDs that have an average diameter between 4 and 5 nm. These new InGaP@ZnS–chitosan nanoparticles emit near the near IR region at 670 nm and are able to penetrate three times deeper into tissue (e.g., even through a mouse skull) while revealing a higher uptake efficiency into PC12 cells with a robust signal. Additionally, a cell viability assay demonstrates that these new fluorescent nanoparticles have good biocompatibility and stability with PC12 cells and neural cells. As a result, these near-IR-emitting nanoparticles can be used for real-time and deep-tissue examination of diverse specimens, such as lymphatic organs, kidneys, hearts, and brains, while leaving the tissue intact.