Carbon Nanotube Optical Reporters for Cancer Drug Discovery

The identification of therapeutic vulnerabilities in cancers has been substantially aided by tools that advance the monitoring of cellular processes and analytes. Our laboratory has developed optical sensors using carbon nanotubes to detect intracellular analytes, including a reporter for lipids that specifically accumulate in the lysosome. Using this reporter, we found that certain cancer cell lines exhibit lysosomal lipid dysfunction and accumulation. We screened a library of lipid-modulating experimental therapeutics using the lipid reporter, finding that the inhibition of some classes of phospholipase enzymes can abrogate the accumulation of lipids in the lysosomes. Follow-up studies found that certain phospholipase enzymes have a protective role in regulating redox stress, and if inhibited can induce cell death in cancer cell lines and in vivo. Our work demonstrated that a carbon nanotube reporter that provides a new type of intracellular measurement can enable target and discovery efforts for the treatment of cancer.