SUMMARY OF INVENTION
Lipid accumulation within the lumen of endolysosomal vesicles is associated with conditions such as cancer, atherosclerosis, liver disease, neurological disorders, and lysosomal storage disorders. Current methods, however, cannot measure lipid flux specifically within the lysosomal lumen of live cells.
MSK investigators have developed an optical reporter capable of detecting lipids, including cholesterol, within the endosomal environment of live cells. This reporter, composed of a photoluminescent carbon nanotube of a single chirality, responds to lipid accumulation via modulation of the nanotube’s optical band gap.
Investigators have demonstrated that the reporter can detect lipid accumulation in the live cells of patients suffering from lysosomal storage disorders (a family of 50 diseases), while also detecting phenotypic reversal in the same cells after drug treatment. Using spectroscopy, the reporter can be utilized in a high throughput drug-screening-type format.
- Breakthrough technology with widespread potential application as an imaging tool or diagnostic
- Novel reporter remains within the endocytic pathway and localizes to the lumen of endolysosomal organelles, without adversely affecting organelle morphology, structural integrity, or function
U.S. National 10,401,295 issued on September 3, 2019. U.S. Continuation 16/548,491 published in December 2019; EUR National published.
As the first technique for measuring lipid flux in the endolysosomal lumen of live cells, this reporter holds the potential for widespread use in both drug screening applications and the investigation of disease pathways associated with altered lipid biology. Possible applications include atherosclerosis, neurodegenerative disease, liver disease, and lysosomal storage disorders.
Jena, PV et al. A Carbon Nanotube Optical Reporter Maps Endolysosomal Lipid Fllux. ACS Nano, 2017 Nov 28;11(11):10689-10703. (PMID: 28898055)
Daniel Heller, PhD, Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering
Eileen Flowers, PhD