Nanomaterial-Based Sensitive Detection for Live Cell Dynamics of Compartmentalized Metabolic Processes

Single-walled carbon nanotubes are promising as biomedical research tools due to their uniquely photostable near-infrared photoluminescence. Complex changes that occur in biological microenvironments should be suitable for interrogation based upon nanotube emission changes. Such changes may be resolved through the use of pharmacological and cell biological techniques to isolate relevant nanotube responses associated with particular biological phenomena. We have designed new chemical functionality into nanomaterials to impart sensitivity towards metabolic flux. Environmentally-controlled in vitro photoluminescence was used to test nanomaterials in conditions that closely mimic conditions found in the cell. We found that these tests were able to afford accurate prediction of the nanomaterial photoluminescence in live cells. In vitro control experiments were closely followed by in-cell measurement during pharmacologic assessment. When the latter method was performed iteratively, we were able to de-convolute the natural background response of nanomaterials in complex cellular systems from biologically relevant and detectable changes. We found that this experimental paradigm was useful to evolve the design of nanomaterials into consistently better detection platforms. With the ability to modulate various characteristics of the nanomaterials, environment-specific responses and location are controllable. These experimental findings are important for future work that aims to measure discreet and temporally distinct biological processes during normal and abnormal cell physiology. The sensors will be used to elucidate mechanisms of drug efficacy and cellular homeostasis.