With the advent of nanotechnology in the diagnosis and treatment of cancer, many questions arise regarding whether novel nanomedicines, nanosensors, and nanoimaging agents are detrimental to living things. At a fundamental level, minute variations in size, shape, and charge can have overwhelming effects on the manner in which a live cell or animal will interact with a nanoparticle. A biomolecular corona, comprising proteins, carbohydrates, lipids, and small molecules, is known to form around nanoparticles and affects everything from the uptake of the nanoparticles into cells to the internal compartmentalization, processing, and eventual expulsion of the nanoparticles from the cells.

The intrinsic band-gap photoluminescence (fluorescence) of single-walled carbon nanotubes (SWCNTs) exhibits exceptional photostability, narrow bandwidth, near-infrared (NIR) tissue-penetrating emission, and microenvironmental sensitivity, enabling their usage in a variety of biomedical imaging and sensing applications. Of recent interest, a biocompatible formulation of carbon nanotubes has been used in the construction of a live-cell lipid accumulation sensor, a condition implicated in a variety of cancers. Additionally, fluorescent carbon nanotubes have been used to interrogate the permeability in multicellular tumor spheroid models. The biological identity of the nanotube sensor inside of the cell has not been thoroughly investigated. Here, by manipulating its composition, we examine the effects that the biomolecular corona has in determining the interactions between carbon nanotubes and live cells. In particular, we study the internalization, processing, toxicity, and long-term fate of the nanomaterial complexes in various types of mammalian cells. With a fundamental mechanistic understanding of the interactions between carbon nanotubes and live cells, we are able to engineer nanosensors with the most reduced toxicities, enhanced stabilities, and highest overall effectiveness.